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Drug Delivery Applications of Metal-Organic Frameworks (MOFs)

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Ashi Mittal, Indrajit Roy and Sona Gandhi

Submitted: 08 February 2022 Reviewed: 14 February 2022 Published: 25 April 2022

DOI: 10.5772/intechopen.103684

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Drug Carriers

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Abstract

There has been substantial progress in the field of metal–organic frameworks (MOFs) and their nanoscale counterparts (NMOFs), in recent years. Their exceptional physicochemical properties are being constantly and actively exploited for various applications such as energy harvesting, gas storage, gas separation, catalysis, etc. Due to their porous framework, large surface area, tunability and easy surface functionalization, MOFs and NMOFs have also emerged as useful tools for biomedical applications, specifically for drug delivery. As drug carriers, they offer high drug loading capacity and controlled release at the target site. This chapter aims to give a panorama of the use of these MOFs as drug delivery agents. A brief overview of the structure and composition of MOFs, along with various methods and techniques to synthesize NMOFs suitable for drug delivery applications are mentioned. In addition, the most commonly employed strategies to associate drugs with these NMOFs are highlighted and methods to characterize them are also briefly discussed. The last section summarizes the applications of MOFs and NMOFs as carriers of therapeutic drugs, biomolecules, and other active agents.

Keywords

  • metal–organic frameworks
  • synthesis
  • drug encapsulation
  • characterization
  • drug delivery
  • biomolecules
  • photosensitizers

1. Introduction

The use of nanomaterials as carriers for the administration of drugs and therapeutic agents is gaining increased attention. These nanocarriers are facilely taken up by the cells and are able to deliver the drug to the target site and prevent its rapid clearance or degradation [1]. Although several inorganic (such as iron oxide NPs, noble metal NPs, quantum dots, etc.) and organic (such as liposomes, polymers, dendrimers) nanomaterials have been produced as nanocarriers, each of these classes of nanomaterials has its own set of merits and demerits [2, 3]. Only a few of these nanosized drug carriers have been approved by the US Food and Drug Administration (FDA); though still, they have some limitations [4].

Metal–organic frameworks (MOFs) also referred to as porous coordination polymers (PCPs) are a crystalline class of coordination polymers and were first reported by Bernard F. Hoskins and Richard Robson in 1989 [5, 6]. MOFs are being synthesized in a building block fashion, in which inorganic building units (metal ion vertices or clusters) are interconnected by organic building units (organic linker molecules) by a self-assembly process, to form highly tailorable crystalline materials having pores in the nanometer range [7]. Their unique combination of high porosity, large surface areas, lack of non-accessible bulk volume, a wide range of pore sizes (micro- or mesopores), shapes (cages, channels, etc.) and topologies, tunable and rigid frameworks, easy surface functionalization, and a limitless number of possible combinations of metals and ligands have resulted in a large number of their potential applications [8, 9].

Nanoscale Metal–organic frameworks or Metal–organic framework nanoparticles (NMOFs or MOF NPs), nanoscale counterparts of MOFs are an attractive class of hybrid nanomaterials. These NMOFs not only exhibit the unique features of porous nanomaterials, but they also have benefits over analogous bulk MOFs for a variety of biomedical applications due to their small size. They can offer many advantages over conventional nanocarriers. (i) First, they can be designed to form desired structures with different shapes, sizes and chemical properties allowing for the loading of various therapeutic agents with different functionalities; (ii) next, their large surface area, high porosity, uniform pore size and volume results in high loading efficiency and selective transport; (iii) further, as a result of their somewhat labile metal and ligand coordination bonds, they are intrinsically biodegradable, which prevents their accumulation in the body after their task is achieved; (iv) finally, their surface functionalization by post-synthetic modifications can improve their colloidal stability, thereby prolonging their blood circulation time [10, 11, 12]. Thus, the miniaturization of MOFs to NMOFs has resulted in the development of nanomaterials with great potential to be used as drug delivery systems. The structural flexibility (referred to as “breathing”) and switchability of MOFs is a unique feature not found in other porous materials [13].

This chapter will give the readers an overview of the use of MOFs and NMOFs as potential drug carriers. In the succeeding sections, the basic composition and structure of these porous frameworks and general synthetic routes adopted for their preparation shall be discussed. Commonly used drug incorporation techniques and characterization methods to verify drug association will also be presented. In the final section, a summary of some of the MOFs and NMOFs reported as carriers and for application in the delivery of therapeutic drugs, biomolecules such as proteins, nucleic acids, carbohydrates, and other active agents employed for light and magnetic field activated therapies, shall be provided.

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2. Structure of MOFs

The design principles of reticular chemistry suggest that deconstruction of a MOF results in four levels of structure [14].

  • The primary structure reveals the chemical composition of MOF, comprising of a metal ion (generally multivalent) and a polydentate organic linker molecule (topicity i.e., points of extension varying between 2 and 12) [15].

  • Secondary building units or SBUs, which are mostly formed in situ, are obtained at the secondary level. These are basically polynuclear metal clusters locking the metal ion into a fixed geometry thereby giving directionality and rigidity to the final MOF structure [16].

  • The tertiary level involves stitching of multiple SBUs together or two metal ions by bridging linkers (having binding groups like phosphates, carboxylates, imidazolates, etc.), giving rise to an internal framework comprising of pores and channels [15].

  • The outer morphology (size and shape) or quaternary structure of MOF depends on the synthesis procedure dictating the growth of the internal framework [17].

Figure 1 depicts the above four levels of MOF structure concerning MOF-5.

Figure 1.

Structure of MOF-5. (a) Primary structure showing composition: metal ion (Zn2+) and linker (terephthalic acid), (b) secondary structure: SBU, Zn4O(-COO)6, (c) tertiary structure: internal framework formed showing linking of SBUs by the terephthalic acid linker, (d) quaternary structure: overall morphology.

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3. Synthesis of NMOFs

Specialized synthetic routes are a prerequisite to obtaining MOFs in the nano-range, ideal for drug administration. The choice of synthesis protocol determines the final size, crystallinity, morphology, uniformity and stability of NMOF. Figure 2 shows a summary of the most often used approaches.

Figure 2.

Schematic representation of various synthetic methods used for the synthesis of NMOFs.

  • Nanoprecipitation is based on the premise that although the precursors (metal ion and linker) are miscible in the original solvent, the formed nanoparticles are either immiscible or can be precipitated out by adding another solvent in which it is not soluble [18].

  • Solvothermal synthesis, performed at higher temperatures results in highly crystalline particles and can be used in combination with surfactants to form surfactant-coated stable particles [19].

  • Reverse microemulsions (sometimes called nanoreactors), which are water-in-oil systems stabilized by appropriate surfactants, can be used as templates to produce monodisperse particles, and size control can be achieved by varying the wo (water: surfactant ratio) value [20].

Other, less commonly used methods include the use of microwaves, ultrasounds, etc. [21, 22]. NMOFs are generally post-synthetically modified or altered to impart them with extra stability, targeting ability, and biocompatibility [23].

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4. Drug incorporation strategies

Some MOFs possess rigid and permanent pores, whereas others are flexible and can respond to external/internal stimuli such as temperature, light, pH, etc. by changing their pore size [24]. In addition, MOFs have distinct features such as breathing, linker rotation, swelling, and subnetwork displacements, which are important for drug loading and release management [25]. There are many ways to associate a drug with MOF, which may be a medicine, a gene, a protein, an enzyme, or any other agent of therapeutic importance.

  • The first approach is to carry out the encapsulation of the drug/therapeutic agent during the synthesis of MOF; this method is referred to as one-pot synthesis [26, 27]. This method can be used to entrap one or more drugs larger than the pore size of MOF and prevents its premature leaching.

  • Another approach is to directly incorporate the prodrug or drug into the framework by using it as a ligand giving higher loading efficiency [28, 29]. The only limitation of this method is that it can lead to loss of therapeutic activity of the incorporated drug.

  • Smaller drugs/cargos can also be post-synthetically encapsulated by introducing them into a dispersion of MOF in a suitable solvent in which they can subsequently diffuse through channels inside MOF pores [30]. This way the drug can also be physically adsorbed on the outer surface by electrostatic interactions.

  • Another method is to post-synthetically associate the drug through covalent bonding with functional groups of organic linkers or by the formation of coordination bonds to metal ions present at coordinatively-unsaturated sites (CUSs) [21, 31, 32, 33, 34]. These CUSs present on the MOF surface behave as Lewis acids and solvent molecules at these sites can be replaced by drugs.

Figure 3 gives a schematic illustration of some of these drug-loading techniques. Multimodal and theranostic systems can also be obtained by using one or more loading techniques to incorporate multiple drugs.

Figure 3.

(a) One-pot synthesis of ZIF-8 NMOF encapsulating zinc phthalocyanine, a photosensitizer used for PDT. Reproduced with permission from [26]. Copyright 2018 American Chemical Society. (b) Direct assembly of porphyrin-based DBC ligand in DBC-UiO NMOF for PDT application. Reproduced with permission from [29]. Copyright 2015 American Chemical Society. (c) Coordinative interaction of His-tags with CUS of MOF: (i) basic MOF molecular composition; (ii) formation of coordinate bond between CUS metal ion (Lewis acid) and imidazolate group of histidine (Lewis base); (iii) generation of multifunctional MOFs by attachment of multiple His-tags. Reproduced with permission from [33]. Copyright 2017 American Chemical Society. (d) Post-synthetic covalent attachment of amino group of DOX to aldehyde of ICA linker in ZIF-90, followed by loading of 5-Fluoro uracil into the pores of NMOF. Reproduced with permission from [34]. Copyright 2017 American Chemical Society.

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5. Characterization

Loading of drugs by MOFs can be confirmed by various methods. Spectroscopic techniques such as UV–visible and fluorescence spectroscopy are useful to confirm encapsulation/loading of chromophoric and fluorescent drugs. Encapsulation of zinc phthalocyanine (ZnPc), which shows characteristic absorbance peaks at 605 and 670 nm was confirmed by the presence of these peaks in the absorbance spectrum of ZnPc@ZIF-8 but absence in the spectrum of only ZIF-8 [26]. This technique is also helpful to quantify the loaded drug. Determination of Brunauer–Emmett–Teller (BET) surface area and pore volume can also help in verifying successful encapsulation of drug. Nitrogen adsorption analysis of ZIF-90, ZIF-90-DOX, and 5-FU@ZIF-90-DOX showed BET surface areas 1045.7, 890.4, and 48.3 m2/g, respectively. A decrease in BET surface area validated drug loading [34]. Deviations in the TGA curve of drug incorporated MOF are also indicative of drug loading. TGA curve of ZIF-90 showed no significant loss in weight between 300 and 500° C, whereas ZIF-90-DOX showed much larger weight loss in the same temperature range. Zeta potential and hydrodynamic size measurement by dynamic light scattering (DLS) experiments can also confirm the nature of the association of MOF with the drug. Pure ZIF-8 nanospheres had a more positive zeta potential value of +31.4 mV, as compared to +22.9 mV for fluorescein adsorbed ZIF-8 nanospheres. This indicated surface adsorption of negatively charged fluorescein dye on the surface of positively charged nanospheres [35]. A very small change in negative zeta potential value for MIL-100 and DM NPs (DOX loaded MIL-100 NPs) confirmed encapsulation of DOX majorly inside the particle with some surface adsorption [36]. Other techniques such as FT-IR spectroscopy, PXRD, NMR, and electron microscopy techniques such as SEM and TEM are also frequently used for characterizing MOFs, with and without drugs [30, 37, 38, 39].

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6. Applications in drug delivery

MOFs are unique inorganic–organic hybrid materials possessing ultrahigh surface area and porosity. They are crystalline, have flexible and rigid frameworks, and also exhibit high chemical and thermal stability. MOFs have been continuously and thoroughly explored and reviewed for numerous applications. Several applications related to MOFs have been reported such as for gas storage and separation, [40, 41, 42] catalysis, [43, 44] sensing, [45] magnetism, [46] and energy [47]. In addition, various biomedical applications have also been reported, including biological sensing, [48] molecular imaging, targeted drug delivery, [21, 49] among others [11].

A large number of side effects are associated with uncontrolled and non-specific drug delivery by direct administration of a free drug inside the body. Great efforts have been made by researchers for the development of methods for targeted, systemic, and controlled drug administration. Nanocarriers have provided a simple and effective solution to this problem. Both organic (such as dendrimers, liposomes, etc.) and inorganic (such as noble metal and metal oxide nanoparticles, quantum dots, silica nanoparticles, etc.) nanocarriers have been reported as potential drug delivery vehicles. Organic nanocarriers such as liposomes are less stable and easily captured by the reticuloendothelial system (RES) once inside the body [50]. Inorganic nanocarriers such as gold, silver, and silica nanoparticles have been reported to be cytotoxic [51]. Inorganic–organic hybrid nanocarriers, such as porous NMOFs, offer many advantages over their pure organic and inorganic counterparts and have established themselves as optimal drug delivery vehicles. In the following subsections, the applications of NMOFs for the delivery and as carriers of therapeutic drugs, biomolecules such as proteins, enzymes, carbohydrates, nucleic acids, and other active agents, shall be discussed briefly.

6.1 Therapeutic drugs

MOFs, owing to their porous structure have been frequently reported for delivery of therapeutic agents such as analgesics, antibiotics, anti-inflammatory and anti-cancer drugs, based on both in vitro and in vivo experiments. In 2006, Horcajada et al. were the first ones to report the ability of MOFs to act as efficient drug delivery agents. They prepared two mesoporous cubic MOFs, namely MIL-100 and MIL-101. They employed them to adsorb ibuprofen, a commonly used anti-inflammatory drug and found that MIL-101 with a larger cage size was able to adsorb more amount of drug (1.4 g/g of MOF) [30]. Nasrabadi et al. reported the use of UiO-66 NMOF with surface area 1196 m2/g to post-synthetically load ciprofloxacin (CIP), an antibiotic. The resulting CIP-UiO-66 NMOF showed a very high drug loading percentage of about 84%, with significant antibacterial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria in comparison to free CIP [52]. ZIF-8 is a pH-responsive MOF, which disintegrates in an acidic environment, and thus is a promising drug carrier especially for anti-cancer applications because of acidic nature of tumor micro-environment. Sun et al. for the first time reported the use of ZIF-8 for the controlled and pH-triggered release of 5-fluorouracil (5-FU), an anticancer drug with high loading capacity (660 mg/g of MOF) [53]. Table 1 summarizes some of the NMOFs and MOFs reported for the delivery of therapeutic agents.

S.No.MOFs/NMOFsMetal ionOrganic linkerTherapeutic drugDrug encapsulation methodReference
a. Analgesics and anti-inflammatory drugs
1.MIL-100Cr3+1,3,5-benzene tricarboxylic acidIbuprofenPost-synthetic encapsulation[30]
2.MIL-101Cr3+1,4-benzene dicarboxylic acidIbuprofenPost-synthetic encapsulation[30]
3.MIL-53Fe3+, Cr3+1,4-benzene dicarboxylic acidIbuprofenPost-synthetic encapsulation[54]
4.MOF-5Zn2+1,4-benzene dicarboxylic acidCurcumin, SulindacPost-synthetic encapsulation[55]
5.ZJU-800Zr2+F-H2PDADiclofenac sodiumPost-synthetic encapsulation[56]
6.M2(olz)Fe2+, Co+2,Ni+2, Zn2+,Mg2+Olsalazine acidOlsalazineDirect assembly[57]
b. Antibacterial and antiviral drugs
1.MIL-101-NH2Fe3+2-amino-1,4-benzene dicarboxylic acidCidofovirPost-synthetic encapsulation[49]
2.UiO-66Zr4+1,4-benzene dicarboxylic acidCiprofloxacinPost-synthetic encapsulation[52]
3.MIL-53Fe3+1,4-benzene dicarboxylic acidVancomycinPost-synthetic encapsulation[58]
4.ZIF-8Zn2+2-methyl imidazolateGentamicinPost-synthetic encapsulation[59]
CiprofloxacinPost-synthetic encapsulation[60]
CeftazidimeOne-pot synthesis[61]
TetracyclineOne-pot synthesis[62]
5.γ-CD-MOFK+CyclodextrinEnrofloxacin, FlorfenicolPost-synthetic encapsulation[63]
6.Bio-MOFMg2+, Mn2+Nalidixic acidNalidixic acidDirect assembly[64]
c. Anti-cancer drugs
1.MIL-100Fe3+1,3,5-benzene tricarboxylic acidBusulfanPost-synthetic encapsulation[49]
DoxorubicinPost-synthetic encapsulation[65]
2.PCN-221Zr4+TCPPMethotrexatePost-synthetic encapsulation[66]
3.NCP-1Tb3+DisuccinatocisplatinCisplatinDirect assembly[28]
4.MIL-89Fe3+Muconic acidDoxorubicinPost-synthetic encapsulation[49]
5.Zn(bix)Zn2+bixDoxorubicin, Camptothecin, DaunomycinOne-pot synthesis[67]
6.UiO-66Zr4+1,4-benzene dicarboxylic acidAlendronateCovalent bonding[32]
7.HKUST-1Cu2+1,3,5-benzene tricarboxylic acidNimesulidePost-synthetic encapsulation[68]
8.ZJU-64Zn2+-adenineTerphenyl dicarboxylic acidMethotrexatePost-synthetic encapsulation[69]
9.ZIF-67Co2+2-methyl imidazolateDoxorubicinOne-pot synthesis[70]
10.Imidazole-2-carboxaldehyde5-Fluoro uracilPost-synthetic encapsulation
[34]
DoxorubicinCovalent bonding
11.ZIF-8Zn2+2-methyl imidazolate5-Fluoro uracilPost-synthetic encapsulation[53]
Camptothecin
Doxorubicin
3-Methyl adenine		One-pot synthesis
One-pot synthesis
One-pot synthesis		[35]
[71]
[27]
12.MOF-5Zn2+1,4-benzene dicarboxylic acidOridoninPost-synthetic encapsulation[72]

Table 1.

Examples of MOFs and NMOFs employed as carriers for therapeutic agents.

6.2 Biomolecules

MOFs have proven themselves as effective carriers for the delivery of large biomolecules such as proteins, enzymes, DNA, RNA, and carbohydrates and small biomolecules such as amino acids, peptides and nucleotides [73]. These biomolecule-MOF composites protect the biodegradation of these biomolecules inside physiological systems and offer a pathway for their safe delivery. Many diseases are a result of protein deficiencies in the body. Also, nucleic acid and carbohydrates based therapies are gaining increasing interest. Intracellular delivery of these biomolecules using MOFs will help in preserving their bioactivity and they will be able to reach their targets avoiding unwanted side effects. There are many methods to form biomolecule-MOF composites. Post-synthetic pore entrapment is the most used method, in which biomolecules smaller than the cavity size of MOF directly diffuse into the pores of the MOF. Chen et al. have demonstrated the use of mesoporous NU-1000 MOF for the entrapment of insulin with high loading (approximately 40%) to treat diabetes mellitus (type 2) [74]. Surface attachment/adsorption is another method that is relatively easy, and biomolecules of all sizes can be attached/adsorbed on the surface via non-covalent interactions such as hydrogen bonding, π-π interactions, Van-der waals interaction, etc. Ni et al. have reported Hf-DBP NMOF for the delivery of αCD47 antibody attached to its surface [75]. Biomolecules can also be covalently linked to MOFs. Wang et al. immobilized dibenzylooctyne (DBCO) appended DNA on UiO-66-N3 through click reaction between DBCO and azide (N3) group [76]. Co-precipitation or one-pot synthesis is another method for biomolecule-MOF composites. The biomolecule is encapsulated during the synthesis of MOF giving high loading and preventing leakage. Shieh et al. used this de novo approach to encapsulate catalase enzyme into the pores of ZIF-90 [77]. Biomimetic mineralization is another in situ encapsulation method in which biomolecules act as templates and nucleation sites for the growth of MOF around them, dictating their final size and morphology. Liang et al. demonstrated the use of various protein, enzyme and DNA templates for the synthesis of MOFs by biomimetic mineralization [38]. Bio-MOFs can also be synthesized by incorporating biomolecules into the framework. Biomolecules have reactive functional groups. They can act as organic linkers and react with metal ions to form bio-MOFs. An et al. synthesized bio-MOF-1 made up of zinc-adeninate clusters and biphenyl dicarboxylic acid. The adenine nucleobase consists of ring N atoms and an amino group that can coordinate with metal ions [78]. Table 2 lists some of the biomolecule-MOF composites.

S.No.MOFs/NMOFsMetal ionOrganic LinkerBiomoleculeIncorporation methodReference
a. Peptides, Proteins, and enzymes
1.NU-1000Zr4+4,4′,4″,4″’-(pyrene-1,3,6,8-tetrayl)tetrabenzoic acidInsulinPost-synthetic entrapment[74]
2.Tb-meso MOFTb3+Triazine-1,3,5-tribenzoic acidCytochrome c

Microperoxidase-11		Post-synthetic entrapment
Post-synthetic entrapment		[79]

[80]
3.MOF-74Zn2+, Mg2+2,5-dioxido terephthalateMyoglobinPost-synthetic entrapment[81]
4.PCN-333Al3+TATBTyrosinasePost-synthetic entrapment[82]
5.ZIF-90Zn2+Imidazole-2-carboxaldehydeCatalaseOne-pot synthesis[77]
6.ZIF-8Zn2+2-methyl imidazolateGlucose oxidase, Horseradish peroxidase
Hemoglobin
Glucose oxidase

Melittin		One-pot synthesis
One-pot synthesis
Biomimetic
Mineralization
One-pot synthesis		[83]
[84]
[85]
[86]
7.Cu-TCCP(Fe)Cu2+TCPP(Fe)Glucose oxidaseSurface attachment[87]
8.MIL-100Fe3+1,3,5-benzene tricarboxylic acidInsulinPost-synthetic encapsulation[88]
b.Antibodies and antigens
1.Hf-DBPHf4+5,15-di(p-benzoato) porphyrinαCD47Surface attachment[75]
2.ZIF-90Zn2+Imidazole-2-carboxaldehydeH-IgG,
G-IgG		One-pot synthesis[89]
3.ZIF-8Zn2+2-methyl imidazolateNivolumabBiomimetic
mineralization		[90]
OvalbuminOne-pot synthesis[91]
4.MIL-100Fe3+1,3,5-benzene tricarboxylic acidanti-EpCAMSurface attachment[92]
5.UiO-AMZr4+1,4-benzene dicarboxylic acid, 2-amino-1,4-benzene dicarboxylic acidOvalbuminSurface attachment[93]
6.Al-MOFAl3+2-amino-1,4-benzene dicarboxylic acidOvalbuminOne-pot synthesis[94]
c. Nucleotides and Nucleic Acids
1.IRMOF-74-IINi2+3,3′-dihydroxy-[1,1′-biphenyl]-4,4′-dicarboxylic acidss-DNAPost-synthetic encapsulation[95]
2.UiO-66-N3Zr4+2-azido-1,4-benzene dicarboxylic acidDBCO-DNACovalent linkage[76]
3.UiO-66Zr4+1,4-benzene dicarboxylic acidTerminal phosphate modified oligo-nucleotidesCovalent linkage[31]
4.ZIF-8Zn2+2-methyl imidazolatePlasmid DNAOne-pot synthesis[96]
5.MIL-101Fe3+1,4-benzene dicarboxylic acidsiRNACovalent-linkage[97]
c. Carbohydrates
1.ZIF-8Zn2+2-methyl imidazolateMeglumine,
Carboxylate dextran
Heparin,
Hyaluronic acid		Biomimetic mineralization
One-pot synthesis		[98]

[99]
2.MAF-7Zn2+3-methyl-1,2,4-triazoleHeparin, Hyaluronic acid, Chondroitin sulfate, Dermatan sulfateOne-pot synthesis[100]

Table 2.

Examples of biomolecule-MOF composites incorporating biomolecules of biological importance.

6.3 Other active agents

Targeted delivery of photoactive compounds such as photosensitizers (dyes, metal nanoparticles/clusters, quantum dots, etc.) incorporated with MOFs and NMOFs can be achieved, preventing their degradation and accumulation in the physiological systems. These compounds are essential for light-activated novel therapies such as photodynamic therapy (PDT) and photothermal therapy (PTT). Xu et al. incorporated a hydrophobic porphyrin-based dye, zinc phthalocyanine inside the pores of ZIF-8 for PDT [26]. Sharma et al. synthesized a bioactive MOF, MB/Cu-GA, for simultaneous PDT and drug delivery. Gallic acid (GA), an anti-cancer agent was directly incorporated into the MOF framework, and the photosensitizer, methylene blue (MB) was post-synthetically encapsulated [101]. Magnetic nanoparticles can also be encapsulated or decorated on the surface of MOF for magneto-cytolytic therapy (magnetic hyperthermia). Chen et al. prepared Fe3O4@PDA@ZIF-90 loaded with DOX nanocomposites for combined magnetic hyperthermia and chemotherapy [102]. Table 3 summarizes some of the examples of MOFs employed for the delivery of photosensitizers and magnetic nanoparticles.

S. No.MOFs/NMOFsMetal ionOrganic linkerActive agentIncorporation methodReference
a. Photodynamic therapy
1.ZIF-8Zn2+2-methyl imidazolateZinc phthalo-cyanine
Chlorin e6
Au nano-clusters		One-pot synthesis


One-pot synthesis
One-pot synthesis		[26]


[103]
[104]
2.MIL-101-NH2Fe3+2-amino-1,4-benzene dicarboxylic acidBlack P quantum dotsOne-pot synthesis[105]
3.DBC-UiOHf4+5,15-di(p-benzoato) chlorinDBCDirect assembly[29]
4.Cu-GACu2+Gallic acidMethylene bluePost-synthetic encapsulation[101]
b. Photothermal therapy
1.ZIF-8Zn2+2-methyl imidazolateCyanine
Graphene quantum dots
Au nano-stars		One-pot synthesis
Surface attachment

One-pot synthesis		[106]
[107]


[108]
2.UiO-66Zr4+1,4-benzene dicarboxylic acidPolyanilineSurface attachment[109]
3.MIL-53Fe3+1,4-benzene dicarboxylic acidPolypyrrole nano-particlesPost-synthetic encapsulation[110]
c. Magneto-cytolytic therapy
1.ZIF-8Zn2+2-methyl imidazolateFe3O4 nano-particlesOne-pot synthesis[102]
2.Fe-MOFFe3+1,4-benzene dicarboxylic acidFe3O4 nano-particlesSurface attachment[111]

Table 3.

Examples of NMOFs and MOFs as carriers of active agents for novel therapies.

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7. Conclusion

This chapter gives a general perspective regarding the use of metal–organic frameworks as drug carriers, in terms of their composition, structure, synthesis, procedures to incorporate drugs and characterization techniques. MOFs are highly porous frameworks with large surface area, made up of repeating units, and generally synthesized by solvothermal and non-solvothermal methods. Therapeutic agents and drugs can be encapsulated, post synthetically attached on the surface, or directly incorporated into the framework. Apart from these compounds, functional biomolecules can also be incorporated with MOFs for the possible treatment of various diseases and therapies. Due to their distinct physicochemical properties, MOFs and NMOFs are gaining prominence for various applications. MOFs have already established themselves as efficient systems for gas storage and separation. Their use as potential drug carriers is relatively new. The available work done by researchers around the world for utilizing these porous frameworks as carriers for drugs will help in synthesizing and designing MOF-drug composites in the future, that can successfully be used for real-world applications.

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Acknowledgments

Ashi Mittal acknowledges fellowship support from the University Grants Commission (UGC), Government of India.

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Conflict of interest

The authors declare no conflict of interest.

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Nomenclature

bix1,4-bis(imidazole-1-ylmethyl)benzene
DBC5,15-di(p-benzoato) chlorin
DBCOdibenzyl cyclooctyne
DBP5,15-di(p-benzoato)porphyrin
F-H2PDA(2E,2′E)- 3,3′-(2-fluoro-1,4-phenylene) diacrylic acid
HKUSTHong Kong University of Science and Technology
ICAImidazole-2-carboxaldehyde
IRMOFIsoreticular Metal Organic Framework
MAFMetal Azolate Framework
MILMaterials Institute Lavoisier
NCPNanoscale coordination polymers
TATB4,4′,4″-s-triazine-2,4,6-triyl-tribenzoic acid
TCPPtetrakis (4- carboxyphenyl) porphyrin
UiOUniversity of Oslo
ZIFZeolitic Imidazolate Framework
ZJUZhejiang University

References

  1. 1. Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacological Reports. 2012;64:1020-1037. DOI: 10.1016/s1734-1140(12)70901-5
  2. 2. Wu MX, Yang YW. Metal-organic framework (mof)-based drug/cargo delivery and cancer therapy. Advanced Materials. 2017;29:e1606134. DOI: 10.1002/adma.201606134
  3. 3. Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nature Reviews. Drug Discovery. 2008;7:771-782. DOI: 10.1038/nrd2614
  4. 4. Anselmo AC, Mitragotri S. Nanoparticles in the clinic: An update. Bioeng Translational Medicine. 2019;4:e10143. DOI: 10.1002/btm2.10143
  5. 5. Luo Z, Fan S, Gu C, Liu W, Chen J, Li B, et al. Metal-organic framework (MOF)-based nanomaterials for biomedical applications. Current Medicinal Chemistry. 2019;26:3341-3369. DOI: 10.2174/0929867325666180214123500
  6. 6. Hoskins BF, Robson R. Infinite polymeric frameworks consisting of three dimensionally linked rod-like segments. Journal of the American Chemical Society. 1989;111:5962-5964. DOI: 10.1021/ja00197a079
  7. 7. Peller M, Böll K, Zimpel A, Wuttke S. Metal-organic framework nanoparticles for magnetic resonance imaging. Inorganic Chemistry Frontiers. 2018;5:1760-1779. DOI: 10.1039/C8QI00149A
  8. 8. Eddaoudi M, Li H, Yaghi OM. Highly porous and stable metal-organic frameworks: structure design and sorption properties. Journal of the American Chemical Society. 2000;122:1391-1397. DOI: 10.1021/ja9933386
  9. 9. Horcajada P, Gref R, Baati T, Allan PK, Maurin G, Couvreur P, et al. Metal-organic frameworks in biomedicine. Chemical Reviews. 2012;112:1232-1268. DOI: 10.1021/cr200256v
  10. 10. Simon-Yarza T, Mielcarek A, Couvreur P, Serre C. Nanoparticles of metal-organic frameworks: on the road to in vivo efficacy in biomedicine. Advanced Materials. 2018;30:e1707365. DOI: 10.1002/adma.201707365
  11. 11. Zhang S, Pei X, Gao H, Chen S, Wang J. Metal-organic framework-based nanomaterials for biomedical applications. Chinese Chemical Letters. 2020;31:1060-1070. DOI: 10.1016/j.cclet.2019.11.036
  12. 12. Riccò R, Liang W, Li S, Gassensmith JJ, Caruso F, Doonan C, et al. Metal-organic frameworks for cell and virus biology: A perspective. ACS Nano. 2018;12:13-23. DOI: 10.1021/acsnano.7b08056
  13. 13. Alhamami M, Doan H, Cheng CH. A review on breathing behaviors of metal-organic-frameworks (MOFs) for gas adsorption. Materials (Basel). 2014;7:3198-3250. DOI: 10.3390/ma7043198
  14. 14. Yaghi OM, O’Keeffe M, Ockwig NW, Chae HK, Eddaoudi M, Kim J. Reticular synthesis and the design of new materials. Nature. 2003;423:705-714. DOI: 10.1038/nature01650
  15. 15. Yaghi OM, Kalmutzki MJ, Diercks CS. Introduction to Reticular Chemistry: Metal-Organic Frameworks and Covalent Organic Frameworks. Wiley; 2019. DOI: 10.1002/9783527821099. Available from: https://onlinelibrary.wiley.com/doi/book/10.1002/9783527821099
  16. 16. Kalmutzki MJ, Hanikel N, Yaghi OM. Secondary building units as the turning point in the development of the reticular chemistry of MOFs. Science Advances. 2018;4:eaat9180. DOI: 10.1126/sciadv.aat9180
  17. 17. Lawson HD, Walton SP, Chan C. Metal-organic frameworks for drug delivery: A design perspective. ACS Applied Materials & Interfaces. 2021;13:7004-7020. DOI: 10.1021/acsami.1c01089
  18. 18. Rocca JD, Liu D, Lin W. Nanoscale metal-organic frameworks for biomedical imaging and drug delivery. Accounts of Chemical Research. 2011;44:957-968. DOI: 10.1021/ar200028a
  19. 19. Butova VV, Soldatov MA, Guda AA, Lomachenko KA, Lamberti C. Metal-organic frameworks: Structure, properties, methods of synthesis and characterization. Russian Chemical Reviews. 2016;85:280-307. DOI: 10.1070/RCR4554
  20. 20. Rieter WJ, Taylor KM, An H, Lin W, Lin W. Nanoscale metal-organic frameworks as potential multimodal contrast enhancing agents. Journal of the American Chemical Society. 2006;128:9024-9025. DOI: 10.1021/ja0627444
  21. 21. Taylor-Pashow KM, Della Rocca J, Xie Z, Tran S, Lin W. Postsynthetic modifications of iron-carboxylate nanoscale metal-organic frameworks for imaging and drug delivery. Journal of the American Chemical Society. 2009;131:14261-14263. DOI: 10.1021/ja906198y
  22. 22. Safarifard V, Morsali A. Applications of ultrasound to the synthesis of nanoscale metal-organic coordination polymers. Coordination Chemistry Reviews. 2015;292:1-14. DOI: 10.1016/j.ccr.2015.02.014
  23. 23. Yang B, Shen M, Liu J, Ren F. Post-synthetic modification nanoscale metal-organic frameworks for targeted drug delivery in cancer cells. Pharmaceutical Research. 2017;34:2440-2450. DOI: 10.1007/s11095-017-2253-9
  24. 24. Uemura K, Matsuda R, Kitagawa S. Flexible microporous coordination polymers. Journal of Solid State Chemistry. 2005;178:2420-2429. DOI: 10.1016/j.jssc.2005.05.036
  25. 25. Nasrollahi M, Nabipour H, Valizadeh N, Mozafari M. The Role of Flexibility in MOFs. Elsevier Inc; 2020. DOI: 10.1016/B978-0-12-816984-1.00006-8. Available from: https://www.sciencedirect.com/science/article/pii/B9780128169841000068?via%3Dihub
  26. 26. Xu D, You Y, Zeng F, Wang Y, Liang C, Feng H, et al. Disassembly of hydrophobic photosensitizer by biodegradable zeolitic imidazolate framework-8 for photodynamic cancer therapy. ACS Applied Materials & Interfaces. 2018;10:15517-15523. DOI: 10.1021/acsami.8b03831
  27. 27. Chen X, Tong R, Shi Z, Yang B, Liu H, Ding S, et al. MOF nanoparticles with encapsulated autophagy inhibitor in controlled drug delivery system for antitumor. ACS Applied Materials & Interfaces. 2017;10:2328-2337. DOI: 10.1021/acsami.7b16522
  28. 28. Rieter WJ, Pott KM, Taylor KM, Lin W. Nanoscale coordination polymers for platinum-based anticancer drug delivery. Journal of the American Chemical Society. 2008;130:11584-11585. DOI: 10.1021/ja803383k
  29. 29. Lu K, He C, Lin W. A chlorin-based nanoscale metal-organic framework for photodynamic therapy of Colon cancers. Journal of the American Chemical Society. 2015;137:7600-7603. DOI: 10.1021/jacs.5b04069
  30. 30. Horcajada P, Serre C, Vallet-Regí M, Sebban M, Taulelle F, Férey G. Metal-organic frameworks as efficient materials for drug delivery. Angewandte Chemie (International Ed. in English). 2006;45:5974-5978. DOI: 10.1002/anie.200601878
  31. 31. Wang S, McGuirk CM, Ross MB, Wang S, Chen P, Xing H, et al. General and direct method for preparing oligonucleotide-functionalized metal-organic framework nanoparticles. Journal of the American Chemical Society. 2017;139:9827-9830. DOI: 10.1021/jacs.7b05633
  32. 32. Zhu X, Gu J, Wang Y, Li B, Li Y, Zhao W, et al. Inherent anchorages in UiO-66 nanoparticles for efficient capture of alendronate and its mediated release. Chemical Communications. 2014;50:8779-8782. DOI: 10.1039/C4CC02570A
  33. 33. Röder R, Preiß T, Hirschle P, Steinborn B, Zimpel A, Höhn M, et al. Multifunctional nanoparticles by coordinative self-assembly of his-tagged units with metal-organic frameworks. Journal of the American Chemical Society. 2017;139:2359-2368. DOI: 10.1021/jacs.6b11934
  34. 34. Zhang FM, Dong H, Zhang X, Sun XJ, Liu M, Yang DD, et al. Postsynthetic modification of ZIF-90 for potential targeted codelivery of two anticancer drugs. ACS Applied Materials & Interfaces. 2017;9:27332-27337. DOI: 10.1021/acsami.7b08451
  35. 35. Zhuang J, Kuo CH, Chou LY, Liu DY, Weerapana E, Tsung CK. Optimized metal-organic-framework nanospheres for drug delivery: Evaluation of small-molecule encapsulation. ACS Nano. 2014;8:2812-2819. DOI: 10.1021/nn406590q
  36. 36. Xue T, Xu C, Wang Y, Wang Y, Tian H, Zhang Y. Doxorubicin-loaded nanoscale metal-organic framework for tumor-targeting and combined chemotherapy and chemodynamic therapy. Biomaterials Science. 2019;7:4615-4623. DOI: 10.1039/C9BM01044K
  37. 37. Lei B, Wang M, Jiang Z, Qi W, Su R, He Z. Constructing redox-responsive metal-organic framework nanocarriers for anticancer drug delivery. ACS Applied Materials & Interfaces. 2018;10:16698-16706. DOI: 10.1021/acsami.7b19693
  38. 38. Liang K, Ricco R, Doherty CM, Styles MJ, Bell S, Kirby N, et al. Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules. Nature Communications. 2015;6:7240. DOI: 10.1038/ncomms8240
  39. 39. Yang Y, Hu Q, Zhang Q, Jiang K, Lin W, Yang Y, et al. A large capacity cationic metal-organic framework nanocarrier for physiological pH responsive drug delivery. Molecular Pharmaceutics. 2016;13:2782-2786. DOI: 10.1021/acs.molpharmaceut.6b00374
  40. 40. Eddaoudi M, Kim J, Rosi N, Vodak D, Wachter J, O’Keeffe M, et al. Systematic deign of pore size and functionality in isoreticular MOFs and their application in methane storage. Science. 2002;295:469-472. DOI: 10.1126/science.1067208
  41. 41. Suh MP, Park HJ, Prasad TK, Lim DW. Hydrogen storage in metal-organic frameworks. Chemical Reviews. 2012;112:782-835. DOI: 10.1021/cr200274s
  42. 42. Sumida K, Rogow DL, Mason JA, McDonald TM, Bloch ED, Herm ZR, et al. Carbon dioxide capture in metal-organic frameworks. Chemical Reviews. 2012;112:724-781. DOI: 10.1021/cr2003272
  43. 43. Seo JS, Whang D, Lee H, Jun SI, Oh J, Jeon YJ, et al. A homochiral metal-organic porous material for enantioselective separation and catalysis. Nature. 2000;404:982-986. DOI: 10.1038/35010088
  44. 44. Lv XL, Wang K, Wang B, Su J, Zou X, Xie Y, et al. A base-resistant metalloporphyrin metal-organic framework for C-H bond halogenation. Journal of the American Chemical Society. 2017;139:211-217. DOI: 10.1021/jacs.6b09463
  45. 45. Li K, He K, Li Q, Xia B, Wang Q, Zhang Y. A zinc(II) MOF based on secondary building units of infinite wavy-shaped chain exhibiting obvious luminescent sense effects. Chinese Chemical Letters. 2019;30:499-501. DOI: 10.1016/j.cclet.2018.05.001
  46. 46. Kurmoo M. Magnetic metal-organic frameworks. Chemical Society Reviews. 2009;38:1353-1379. DOI: 10.1039/B804757J
  47. 47. Zhang T, Lin W. Metal-organic frameworks for artificial photosynthesis and photocatalysis. Chemical Society Reviews. 2014;43:5982-5993. DOI: 10.1039/C4CS00103F
  48. 48. Ling P, Lei J, Zhang L, Ju H. Porphyrin-encapsulated metal-organic frameworks as mimetic catalysts for electrochemical DNA sensing via allosteric switch of hairpin DNA. Analytical Chemistry. 2015;87:3957-3963. DOI: 10.1021/acs.analchem.5b00001
  49. 49. Horcajada P, Chalati T, Serre C, Gillet B, Sebrie C, Baati T, et al. Porous metal-organic frameworks nanoscale carriers as a potential platform for drug delivery and imaging. Nature Materials. 2010;9:172-179. DOI: 10.1038/nmat2608
  50. 50. Ishida T, Harashima H, Kiwada H. Liposome Clearance. Bioscience Reports. 2002;22:197-224. DOI: 10.1023/A:1020134521778
  51. 51. Soenen SJ, Parak WJ, Rejman J, Manshian B. (Intra) cellular stability of inorganic nanoparticles: effects on cytotoxicity, particle functionality, and biomedical applications. Chemical Reviews. 2015;115:2109-2135. DOI: 10.1021/cr400714j
  52. 52. Nasrabadi M, Ghasemzadeh MA, Zand Monfared MR. The preparation and characterization of UiO-66 metal-organic frameworks for the delivery of the drug ciprofloxacin and an evaluation of their antibacterial activities. New Journal of Chemistry. 2019;43:16033-16040. DOI: 10.1039/C9NJ03216A
  53. 53. Sun CY, Qin C, Wang XL, Yang GS, Shao KZ, Lan YQ, et al. Zeolitic imidazolate framework-8 as efficient pH-sensitive drug delivery vehicle. Dalton Transactions. 2012;41:6906-6909. DOI: 10.1039/C2DT30357D
  54. 54. Horcajada P, Serre C, Maurin G, Ramsahye NA, Balas F, Vallet-Regí M, et al. Flexible porous metal-organic frameworks for a controlled drug delivery. Journal of the American Chemical Society. 2008;130:6774-6780. DOI: 10.1021/ja710973k
  55. 55. Suresh K, Matzger AJ. Enhanced drug delivery by dissolution of amorphous drug encapsulated in a water unstable metal-organic framework (MOF). Angewandte Chemie (International Ed. in English). 2019;58:16790-16794. DOI: 10.1002/anie.201907652
  56. 56. Jiang K, Zhang L, Hu Q, Zhao D, Xia T, Lin W, et al. Pressure controlled drug release in a Zr-cluster-based MOF. Journal of Materials Chemistry B. 2016;4:6398-6401. DOI: 10.1039/C6TB01756H
  57. 57. Levine DJ, Runčevski T, Kapelewski MT, Keitz BK, Oktawiec J, Reed DA, et al. Olsalazine-based metal-organic frameworks as biocompatible platforms for H2 adsorption and drug delivery. Journal of the American Chemical Society. 2016;138:10143-10150. DOI: 10.1021/jacs.6b03523
  58. 58. Lin S, Liu X, Tan L, Cui Z, Yang X, Yeung KWK, et al. Porous iron-carboxylate metal-organic framework: A novel bioplatform with sustained antibacterial efficacy and nontoxicity. ACS Applied Materials & Interfaces. 2017;9:19248-19257. DOI: 10.1021/acsami.7b04810
  59. 59. Soltani B, Nabipour H, Nasab NA. Efficient storage of gentamicin in nanoscale zeolitic imidazolate framework-8 nanocarrier for pH-responsive drug release. Journal of Inorganic and Organometallic Polymers and Materials. 2018;28:1090-1097. DOI: 10.1007/s10904-017-0745-z
  60. 60. Nabipour H, Sadr MH, Bardajee GR. Synthesis and characterization of nanoscale zeolitic imidazolate frameworks with ciprofloxacin and their applications as antimicrobial agents. New Journal of Chemistry. 2017;41:7364-7370. DOI: 10.1039/C7NJ00606C
  61. 61. Sava Gallis DF, Butler KS, Agola JO, Pearce CJ, McBride AA. Antibacterial countermeasures via metal-organic framework-supported sustained therapeutic release. ACS Applied Materials & Interfaces. 2019;11:7782-7791. DOI: 10.1021/acsami.8b21698
  62. 62. Zhang X, Liu L, Huang L, Zhang W, Wang R, Yue T, et al. The highly efficient elimination of intracellular bacteria via a metal organic framework (MOF)-based three-in-one delivery system. Nanoscale. 2019;11:9468-9477. DOI: 10.1039/C9NR01284B
  63. 63. Wei Y, Chen C, Zhai S, Tan M, Zhao J, Zhu X, et al. Enrofloxacin/florfenicol loaded cyclodextrin metal-organic-framework for drug delivery and controlled release. Drug Delivery. 2021;28:372-379. DOI: 10.1080/10717544.2021.1879316
  64. 64. André V, da Silva ARF, Fernandes A, Frade R, Garcia C, Rijo P, et al. Mg- and Mn-MOFs boost the antibiotic activity of nalidixic acid. ACS Applied Bio Materials. 2019;2:2347-2354. DOI: 10.1021/acsabm.9b00046
  65. 65. Anand R, Borghi F, Manoli F, Manet I, Agostoni V, Reschiglian P, et al. Host-guest interactions in Fe(III)-trimesate MOF nanoparticles loaded with doxorubicin. The Journal of Physical Chemistry. B. 2014;118:8532-8539. DOI: 10.1021/jp503809w
  66. 66. Lin W, Hu Q, Jiang K, Yang Y, Yang Y, Cui Y, et al. A porphyrin-based metal-organic framework as a pH-responsive drug carrier. Journal of Solid State Chemistry. 2016;237:307-312. DOI: 10.1016/j.jssc.2016.02.040
  67. 67. Imaz I, Rubio-Martínez M, García-Fernández L, García F, Ruiz-Molina D, Hernando J, et al. Coordination polymer particles as potential drug delivery systems. Chemical Communications. 2010;46:4737-4739. DOI: 10.1039/C003084H
  68. 68. Ke F, Yuan YP, Qiu LG, Shen YH, Xie AJ, Zhu JF, et al. Facile fabrication of magnetic metal-organic framework nanocomposites for potential targeted drug delivery. Journal of Materials Chemistry. 2011;21:3843-3848. DOI: 10.1039/C0JM01770A
  69. 69. Lin W, Hu Q, Yu J, Jiang K, Yang Y, Xiang S, et al. Low cytotoxic metal-organic frameworks as temperature-responsive drug carriers. ChemPlusChem. 2016;81:804-810. DOI: 10.1002/cplu.201600142
  70. 70. Gao S, Jin Y, Ge K, Li Z, Liu H, Dai X, et al. Self-supply of O2 and H2O2 by a nanocatalytic medicine to enhance combined chemo/chemodynamic therapy. Advancement of Science. 2019;6:1902137. DOI: 10.1002/advs.201902137
  71. 71. Zheng H, Zhang Y, Liu L, Wan W, Guo P, Nyström AM, et al. One-pot synthesis of metal-organic frameworks with encapsulated target molecules and their applications for controlled drug delivery. Journal of the American Chemical Society. 2016;138:962-968. DOI: 10.1021/jacs.5b11720
  72. 72. Chen G, Luo J, Cai M, Qin L, Wang Y, Gao L, et al. Investigation of metal-organic framework-5 (MOF-5) as an antitumor drug oridonin sustained release carrier. Molecules. 2019;24:3369. DOI: 10.3390/molecules24183369
  73. 73. An H, Li M, Gao J, Zhang Z, Ma S, Chen Y. Incorporation of biomolecules in metal-organic frameworks for advanced applications. Coordination Chemistry Reviews. 2019;384:90-106. DOI: 10.1016/j.ccr.2019.01.001
  74. 74. Chen Y, Li P, Modica JA, Drout RJ, Farha OK. Acid-resistant mesoporous metal-organic framework toward oral insulin delivery: Protein encapsulation, protection, and release. Journal of the American Chemical Society. 2018;140:5678-5681. DOI: 10.1021/jacs.8b02089
  75. 75. Ni K, Luo T, Culbert A, Kaufmann M, Jiang X, Lin W. Nanoscale metal-organic framework co-delivers TLR-7 agonists and anti-CD47 antibodies to modulate macrophages and orchestrate cancer immunotherapy. Journal of the American Chemical Society. 2020;142:12579-12584. DOI: 10.1021/jacs.0c05039
  76. 76. Morris W, Briley WE, Auyeung E, Cabezas MD, Mirkin CA. Nucleic acid-metal organic framework (MOF) nanoparticle conjugates. Journal of the American Chemical Society. 2014;136:7261-7264. DOI: 10.1021/ja503215w
  77. 77. Shieh FK, Wang SC, Yen CI, Wu CC, Dutta S, Chou LY, et al. Imparting functionality to biocatalysts via embedding enzymes into nanoporous materials by a de novo approach: size-selective sheltering of catalase in metal-organic framework microcrystals. Journal of the American Chemical Society. 2015;137:4276-4279. DOI: 10.1021/ja513058h
  78. 78. An J, Geib SJ, Rosi NL. Cation-triggered drug release from a porous zinc-adeninate metal-organic framework. Journal of the American Chemical Society. 2009;131:8376-8377. DOI: 10.1021/ja902972w
  79. 79. Chen Y, Lykourinou V, Vetromile C, Hoang T, Ming LJ, Larsen RW, et al. How can proteins enter the interior of a MOF? investigation of cytochrome c translocation into a MOF consisting of mesoporous cages with microporous windows. Journal of the American Chemical Society. 2012;134:13188-13191. DOI: 10.1021/ja305144x
  80. 80. Lykourinou V, Chen Y, Wang XS, Meng L, Hoang T, Ming LJ, et al. Immobilization of MP-11 into a mesoporous metal-organic framework, MP-11@mesoMOF: A new platform for enzymatic catalysis. Journal of the American Chemical Society. 2011;133:10382-10385. DOI: 10.1021/ja2038003
  81. 81. Deng H, Grunder S, Cordova KE, Valente C, Furukawa H, Hmadeh M, et al. Large-pore apertures in a series of metal-organic frameworks. Science. 2012;336:1018-1023. DOI: 10.1126/science.1220131
  82. 82. Lian X, Huang Y, Zhu Y, Fang Y, Zhao R, Joseph E, et al. Enzyme-MOF nanoreactor activates nontoxic paracetamol for cancer therapy. Angewandte Chemie (International Ed. in English). 2018;57:5725-5730. DOI: 10.1002/anie.201801378
  83. 83. Wu X, Ge J, Yang C, Hou M, Liu Z. Facile synthesis of multiple enzyme-containing metal-organic frameworks in a biomolecule-friendly environment. Chemical Communications. 2015;51:13408-13411. DOI: 10.1039/C5CC05136C
  84. 84. Peng S, Liu J, Qin Y, Wang H, Cao B, Lu L, et al. Metal-organic framework encapsulating hemoglobin as high-stable and long-circulating oxygen carriers o treat hemorrhagic shock. ACS Applied Materials & Interfaces. 2019;11:35604-35612. DOI: 10.1021/acsami.9b15037
  85. 85. Zhang X, Zeng Y, Zheng A, Cai Z, Huang A, Zeng J, et al. A fluorescence based immunoassay for galectin-4 using gold nanoclusters and a composite consisting of glucose oxidase and a metal-organic framework. Microchimica Acta. 2017;184:1933-1940. DOI: 10.1007/s00604-017-2204-5
  86. 86. Li Y, Xu N, Zhu W, Wang L, Liu B, Zhang J, et al. Nanoscale Melittin@Zeolitic imidazolate frameworks for enhanced anticancer activity and mechanism analysis. ACS Applied Materials & Interfaces. 2018;10:22974-22984. DOI: 10.1021/acsami.8b06125
  87. 87. Liu X, Yan Z, Zhang Y, Liu Z, Sun Y, Ren J, et al. Two-dimensional metal-organic framework/enzyme hybrid nanocatalyst as a benign and self-activated Cascade reagent for in vivo wound healing. ACS Nano. 2019;13:5222-5230. DOI: 10.1021/acsnano.8b09501
  88. 88. Zhou Y, Liu L, Cao Y, Yu S, He C, Chen X. A nanocomposite vehicle based on metal-organic framework nanoparticle incorporated biodegradable microspheres for enhanced oral insulin delivery. ACS Applied Materials & Interfaces. 2020;12:22581-22592. DOI: 10.1021/acsami.0c04303
  89. 89. Feng Y, Wang H, Zhang S, Zhao Y, Gao J, Zheng Y, et al. Antibodies@MOFs: An in vitro protective coating for preparation and storage of biopharmaceuticals. Advanced Materials. 2018;31:1805148. DOI: 10.1002/adma.201805148
  90. 90. Alsaiari SK, Qutub SS, Sun S, Baslyman W, Aldehaiman M, Alyami M, et al. Sustained and targeted delivery of checkpoint inhibitors by metal-organic frameworks for cancer immunotherapy. Science Advances. 2021;7:eabe7174. DOI: 10.1126/sciadv.abe7174
  91. 91. Zhang Y, Wang F, Ju E, Liu Z, Chen Z, Ren J, et al. Metal-organic framework-based vaccine platforms for enhanced systemic immune and memory response. Advanced Functional Materials. 2016;26:6454-6461. DOI: 10.1002/adfm.201600650
  92. 92. Xie W, Yin T, Chen YL, Zhu DM, Zan MH, Chen B, et al. Capture and “self-release” of circulating tumor cells using metal-organic framework materials. Nanoscale. 2019;11:8293-8303. DOI: 10.1039/C8NR09071H
  93. 93. Qi Y, Wang L, Guo H, Pan Y, Xie Z, Jin N, et al. Antigen-enabled facile preparation of MOF nanovaccine to activate the complement system for enhanced antigen-mediated immune response. Biomaterials Science. 2019;7:4022-4026. DOI: 10.1039/C9BM01145E
  94. 94. Miao YB, Pan WY, Chen KH, Wei HJ, Mi FL, Lu MY, et al. Engineering a nanoscale Al-MOF-armored antigen carried by a “Trojan Horse”-like platform for oral vaccination to induce potent and long-lasting immunity. Advanced Functional Materials. 2019;29:1904828. DOI: 10.1002/adfm.201904828
  95. 95. Peng S, Bie B, Sun Y, Liu M, Cong H, Zhou W, et al. Metal-organic frameworks for precise inclusion of single-stranded DNA and transfection in immune cells. Nature Communications. 2018;9:1293. DOI: 10.1038/s41467-018-03650-w
  96. 96. Li Y, Zhang K, Liu P, Chen M, Zhong Y, Ye Q, et al. Encapsulation of plasmid DNA by nanoscale metal-organic frameworks for efficient gene transportation and expression. Advanced Materials. 2019;31:1901570. DOI: 10.1002/adma.201901570
  97. 97. Chen Q, Xu M, Zheng W, Xu T, Deng H, Liu J. Se/Ru-decorated porous metal-organic framework nanoparticles for the delivery of pooled siRNAs to reversing multidrug resistance in taxol-resistant breast cancer cells. ACS Applied Materials & Interfaces. 2017;9:6712-6724. DOI: 10.1021/acsami.6b12792
  98. 98. Astria E, Thonhofer M, Ricco R, Liang W, Chemelli A, Tarzia A, et al. Carbohydrates@MOFs. Materials Horizons. 2019;6:969-977. DOI: 10.1039/C8MH01611A
  99. 99. Zheng J, Li B, Ji Y, Chen Y, Lv X, Zhang X, et al. Prolonged release and shelf-life of anticoagulant sulfated polysaccharides encapsulated with ZIF-8. International Journal of Biological Macromolecules. 2021;183:1174-1183. DOI: 10.1016/j.ijbiomac.2021.05.007
  100. 100. Velásquez-Hernández MDJ, Astria E, Winkler S, Liang W, Wiltsche H, Poddar A, et al. Modulation of metal-azolate frameworks for the tunable release of encapsulated glycosaminoglycans. Chemical Science. 2020;11:10835-10843. DOI: 10.1039/D0SC01204A
  101. 101. Sharma S, Mittal D, Verma AK, Roy I. Copper-gallic acid nanoscale metal-organic framework for combined drug delivery and photodynamic therapy. ACS Applied Bio Materials. 2019;2:2092-2101. DOI: 10.1021/acsabm.9b00116
  102. 102. Chen J, Liu J, Hu Y, Tian Z, Zhu Y. Metal-organic framework-coated magnetite nanoparticles for synergistic magnetic hyperthermia and chemotherapy with pH-triggered drug release. Science and Technology of Advanced Materials. 2019;20:1043-1054. DOI: 10.1080/14686996.2019.1682467
  103. 103. Sun Q, Bi H, Wang Z, Li C, Wang C, Xu J, et al. O2-generating metal-organic framework-based hydrophobic photosensitizer delivery system for enhanced photodynamic therapy. ACS Applied Materials & Interfaces. 2019;11:36347-36358. DOI: 10.1021/acsami.9b11607
  104. 104. Zhang L, Gao Y, Sun S, Li Z, Wu A, Zeng L. pH-Responsive metal-organic framework encapsulated gold nanoclusters with modulated release to enhance photodynamic therapy/chemotherapy in breast cancer. Journal of Materials Chemistry B. 2020;8:1739-1747. DOI: 10.1039/C9TB02621E
  105. 105. Liu J, Liu T, Du P, Zhang L, Lei J. Metal-organic framework (MOF) hybrid as a tandem catalyst for enhanced therapy against hypoxic tumor cells. Angewandte Chemie (International Ed. in English). 2019;58:7808-7812. DOI: 10.1002/anie.201903475
  106. 106. Li Y, Xu N, Zhou J, Zhu W, Li L, Dong M, et al. Facile synthesis of a metal-organic framework nanocarrier or NIR imaging-guided photothermal therapy. Biomaterials Science. 2018;6:2918-2924. DOI: 10.1039/C8BM00830B
  107. 107. Tian Z, Yao X, Ma K, Niu X, Grothe J, Xu Q, et al. Metal-organic framework/graphene quantum dot nanoparticles used for synergistic chemo- and photothermal therapy. ACS Omega. 2017;2:1249-1258. DOI: 10.1021/acsomega.6b00385
  108. 108. Deng X, Liang S, Cai X, Huang S, Cheng Z, Shi Y, et al. Yolk-shell structured Au nanostar@metal-organic framework for synergistic chemo-photothermal therapy in the second near-infrared window. Nano Letters. 2019;19:6772-6780. DOI: 10.1021/acs.nanolett.9b01716
  109. 109. Wang W, Wang L, Li Y, Liu S, Xie Z, Jing X. Nanoscale polymer metal-organic framework hybrids for effective photothermal therapy of Colon cancers. Advanced Materials. 2016;28:9320-9325. DOI: 10.1002/adma.201602997
  110. 110. Huang J, Li N, Zhang C, Meng Z. Metal-organic framework as a microreactor for in situ fabrication of multifunctional nanocomposites for photothermal-chemotherapy of tumors in vivo. ACS Applied Materials & Interfaces. 2018;10:38729-38738. DOI: 10.1021/acsami.8b12394
  111. 111. Xiang Z, Qi Y, Lu Y, Hu Z, Wang X, Jia W, et al. MOF-derived novel porous Fe3O4@C nanocomposites as smart nanomedical platforms or combined cancer therapy: magnetic-triggered synergistic hyperthermia and chemotherapy. Journal of Materials Chemistry B. 2020;8:8671-8683. DOI: 10.1039/D0TB01021A

Written By

Ashi Mittal, Indrajit Roy and Sona Gandhi

Submitted: 08 February 2022 Reviewed: 14 February 2022 Published: 25 April 2022

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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