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In case cancers are located deep inside the body and are very tough to diagnose, diagnostic tools like MRI/CT scans can be employed to detect these cancers. The major challenge in such cases is the delivery of MRI active agents or visualizing agents to the target site. In this context we will discuss different mesoporous nanoparticles that can be employed to target the tissue at a specific location, its functionalization to reach the target site (Folic acid), different simple dyes as well as specific dyes which offer theranostic functionality. The nanoparticles like mesoporous silica nanoparticles offer the possibility to load therapeutic and diagnostic agents. Its surface allow multiple functionalization and conjugations which offer target specific delivery of these agents. Moreover we will also overview different modern drug delivery inventions for offering theranostic application.
Rastriya Shikshan Mandal NN Sattha College of Pharmacy, India
Vishal Pande
Rastriya Shikshan Mandal NN Sattha College of Pharmacy, India
*Address all correspondence to: ajinkyapote1996@gmail.com
1. Introduction
Sporadic and wild cell development is profoundly connected with malignant growth. With metastasis and intrusion-related to harmful phenotypic conduct, malignancy forcefully assaults different territories of the human body and is broadly accepted to be one of the most dependable illnesses throughout the world Over the previous decade, the rate and passing rate related to disease have risen pointedly. As indicated by the 2015 World Health Organization figures, malignancy is one of the central reasons for death in industrialized countries. In unindustrialized countries, it is second just to cardiovascular illness as the primary driver of death. It is Expectable that by 2020, the number of progress from a disease will include 13% of the all-out through the world. Current threatening cell treatment models, for example, chemotherapy, medical procedure, photodynamic treatment (PDT), and radiotherapy, are fit for dragging out a patient’s life somewhat and helping them to live more. In any case, radiotherapy has hindering impacts, for example, the danger of minor threat at the uncovered zone, and it can venture to such an extreme as to harm live and solid tissues. Chemotherapy is portrayed by the utilization of an assortment of chemotherapeutic specialists to slaughter disease cells and stop its expansion. Various chemotherapeutic specialists are not cell-explicit and, in this way, are fit for pulverizing ordinary cells and further adding to perpetual fundamental issues. Notwithstanding not being cell-explicit, the aggravation of multidrug obstruction, displayed by most malignant growth cells, acts as a genuine restriction and adds to the low restorative list of chemotherapy. One promising, rising order is nanomedicine, which incorporates nanotechnology and biomedicine [1]. Nanomedicine has incredible potential for growing the therapy of different infirmities, including diabetes, tissue designing, and heart sicknesses, just as extraordinary possible applications in disease theranostics. The fast development of novel nanomaterials has become an extraordinary stage for defeating the unfriendly impacts of chemotherapy, even without the most punctual stage determination of malignancy. In this way, wonderful methodologies have been taken to create nanomaterials for malignancy theranostics. Bio-imaging combined with malignant growth treatment has been shown by Loo et al., who created nanoshells focused on the insusceptible framework to recognize and slaughter bosom disease cells. Different investigations have likewise made monstrous forward leaps. Similarly, mesoporous silica nanomaterials (MSNs) have extraordinary potential as functionalized nanoparticles [2]. An early case of their utility included a cycle in which folic acid (FA) was combined, and changed MSNs were utilized for a focused exchange of the water-safe anticancer prescription camptothecin. In entirety, the examination performed has uncovered that mesoporous silica nanoplexes have significant in vitro and in vivo disease obliteration abilities, and they have applications in imaging and malignant growth treatment at the same time as the investigation into nanomaterials keeps on rising, nanomedicine as a field of study is anticipated to serve a significant part in malignancy analysis and treatment. Silica is one of the pinnacle regular assets accessible on earth and assumes a significant part in medication, primarily regarding human skin and bones, etc. Sorted by the FDA as for the most part perceived as protected generally recognized as safe (GRAS), silicon dioxide is commonly utilized as a food added substance and in the beauty care products and drug businesses. Due to the part of silica in soothing biosafety concerns and the simplicity of the cycles engaged with the manufacture of silica, silica nanomaterials assume an extremely indispensable function in biomedical investigations. In the course of the most recent decade, mesoporous nanomaterials have pulled in developing consideration in the fields of optical imaging, magnetic resonance imaging (MRI), photodynamic treatment, and medication conveyance. MSNs show more wide-running possibilities than other medication conveyance frameworks and offer empowering justification for simultaneous disease determination and treatment, just as medication (Table 1) [3, 4].
2. Introduction of cancer including types and treatment available
Body is made up of millions of tiny cells, each of which is a separate living organism. Usually, each cell attaches to the other, including the tissues and organs of your body. One way in which this interaction occurs is seen in the way your cells reproduce. Normal cells in the body grow and divide over time and then stop growing and dividing. Thereafter, they present themselves as needed to replace defective or dying cells. Cancer occurs when the cell production process is out of control. In other words, cancer is a disease characterized by uncontrolled, irregular and irregular cell division. Unlike normal cells, cancer cells continue to grow and divide throughout life, replicating themselves into more dangerous cells [5].
The abnormal growth and differentiation seen in cancer cells is caused by damage to these DNA in cells. There are various ways in which cellular DNA can be altered and gets defective. For example, environmental factors, such as exposure to smoke can trigger a series of events leading to change in normal cellular DNA and that causes cancer. Alternatively, faulty DNA can be inherited from your parents.
As cancer cells divide and multiply, they often form a combination of cancer cells called tumors. Tissues cause many symptoms of cancer by suppressing, crushing, and destroying non-cancerous cells and tissues The currently available treatment for carcinoma is surgery, radiation therapy, chemotherapy, immunotherapy to treat cancer, targeted therapy, Hormone therapy, Stem cell transplant, precision medicine [5].
Surgery: The surgery may be carried out by giving either local anesthesia, regional anesthesia, general anesthesia and physical giving cut and removing the tumor. The other options available are Cryosurgery, Laser, Hyperthermia, Photodynamic Therapy.
Radiation therapy: It is a cancer therapy that involves the use of focused radiation beams to destroy cancer cells and shrink tumors. External beam treatment is the most prevalent method of radiation therapy. A equipment that focuses high-energy radiation beams onto cancer cells is used in this sort of treatment. Radiation may be aimed to precise locations with this device.
Chemotherapy: Chemotherapy causes cell division to be disrupted. The nucleus, located at the centre of each live cell, is the cell’s control centre. It is made up of chromosomes, which carry genes. Each time a cell divides into two to generate new cells, these genes must be duplicated exactly. Chemotherapy causes genetic harm in the nucleus of cells. Some medications cause harm to cells when they divide. Some cause harm to cells when they duplicate all of their DNA before splitting. Chemotherapy has a lower risk of harming cells that are dormant, such as most normal cells. Chemotherapy medicines are frequently used in combination. This will include medications that harm cells at various phases of the cell division process.
Immunotherapy: Immunotherapy is a form of cancer treatment which helps combat cancer in your immune system. Your body is supported by the immune system to prevent viruses and other diseases. It is composed of lymph system white blood cells and organs and tissues. Immunotherapy is a biological form of treatment. Biological therapy is a method of medicine used to cure cancer by using medicines created from living organisms.
Targeted Therapy: Targeted therapies are either small-molecule drugs or monoclonal antibodies. The functionalised nanoparticles are able to deliver the molecules to the targeted sites, i.e., API/another chemotherapeutics.
Hormone therapy: it is a form of systemic therapy—a way of administering drugs so they travel throughout the body, rather than being delivered directly to the cancer—that works to add, block or remove hormones from the body to slow or stop the growth of cancer cells.
Stem Cell Transplant: A stem cell transplant (also known as a bone marrow transplant) is a procedure in which defective or cancerous bone marrow is replaced with new, healthy bone marrow cells. A stem cell transplant may be used to treat leukemia and lymphoma, cancers that affect the blood and lymphatic system.
There are two types of stem cell transplantation:
Autologous stem cell transplant:
Healthy cells are isolated from bone marrow of patients. The bone marrow taken from the person initially frozen till it is ready to use. Meanwhile, patient prepare their body for conditioning regimen for transplant. In this process he may receive high dose of multiple therapies and these treatments destroys cancer cells but they also kill bone marrow cells. The patient is injected with their own stored blood stem cells. These cells restore ability to produce blood cells in body.
Allogeneic stem cell transplant:
In this type, the donor stem cells are injected in patient when he has undergone chemotherapy. The allogeneic stem cell transplantation can help fight cancer directly. The cells donated by person they generate new immune response in patient (they find and kill cancer cells) this immune response generated by new cells is better than original immune cells [3].
Medical services foundation in developing business sectors, nonetheless, has not stayed up with the ascent in non-transferable maladies, particularly malignancy. Verifiable wellbeing needs, for example, adolescence and transferable maladies remain needs, in front of malignancy, ceaseless infections, and different ailments of maturing. Given restricted assets and fixed government medical care financial plans, general wellbeing frameworks face extensive difficulties in conveying convenient finding and therapy to malignancy patients [1].
3.1 Challenges for targeted therapies in cancer treatment
The advancing our comprehension of the sub-atomic pathway that direct cell development, apoptosis, angiogenesis and metastasis, and the correspondence or cross-talk between these transformed pathways and receptors [6].
Several critical steps need to be realized in the application of targeted therapies in malignant growth control:
Developing clinically helpful prognostic markers to distinguish individual requiring treatment.
Developing prescient markers that distinguish and select people who will profit most from these treatments.
Avoiding treatment in those improbable to react or in danger of inadmissible harmfulness.
Combining operators that target distinctive key pathways.
Combining specialists with regular treatments.
Developing techniques to conquer procured obstruction [7].
Clinical preliminaries are fundamental and assume a key function intending to this issue.
The trublesomes of the targeted therapy is that the results are not always as expected. However the assurance of targeted therapy are self-evident, its challenges are not as conspicuous. To accomplish the promises and commensurate the challenges of targeted therapy, one needs to look at the basics of cancer biology. As a initiators, one has to unfold the mystery of driver mutations, intra-tumoural heterogeneity and cancer subtypes.
3.2 Challenges involved in cancer immunotherapy
The approach to cancer immunotherapy involves harnessing the specificity and killing mechanisms of the immune system to target and extirpate malignant cells.
To apply immunotherapies to a larger demography of patients, more conserved indicators expressed on the surface of tumor cells must be found. The purpose of active immunotherapy is to target a particular sequence known as “neoantigens” or tumor-specific antigens that is only expressed on tumor cells (TSA). However, many of the antigens found on tumors are also found on healthy cells, making any therapy including a nontumor specific antigen deadly to healthy cells. Identifying TSA targets for immunotherapy would almost certainly result in improved treatment results with minimum harm to healthy cells. The cancer-testis antigens (CTAs), which are expressed more easily on cancer cells than on healthy ones, are one example of a possible target. Another feature of these antigens is that they generate a strong immunological response. Cancer stem cells, a secretive subgroup of the tumor that contributes to its ability to self-renew continuously even after therapeutic intervention, also express CTAs. Identifying additional markers would therefore assist to overcome the problems given by tumor heterogeneity, since the likelihood of targeting more than one kind of cell would be improved if the host immune cells were “trained” to detect several antigens and launch a vigorous attack on the entire tumor [8].
Due to the development of metabolomics and imaging detection technology, the complex metabolic changes that are involved in the occurrence and development of tumors have become increasingly clear. Metabolic control is a potent weapon that the tumor can employ to break through the growth barrier, as well as a basic activity throughout tumor growth. The tumor’s flexible and complex metabolic patterns can promote tumor adaptation to different microenvironments while also contributing to the secretion of inflammatory factors that inhibit immune cell function in the microenvironment and, as a result, interfere with normal metabolism in the body, creating an environment that promotes tumor cell malignancy. Furthermore, tumor cells and normal cells overlap metabolic pathways, making it challenging to intervene in tumor metabolism without impacting normal cells. As a result, there are still several challenges in the targeted therapy of tumor metabolism, as well as numerous concerns in the field of tumor metabolic control. Active peptides typically have 2 to 30 amino acid residues and have beneficial properties such as strong curative effects, reduced side effects, small molecular weights, and easy absorption, which enable them to specifically bind to tumor tissues and interact with tumor growth-related and metastasis-related signal transduction molecules to inhibit tumor growth and metastasis and promote apoptosis in tumor cells. The PI3K/AKT/mTOR, AMPK, STAT3, TRAIL death receptor, and NF-кB signaling pathways are all implicated in tumor metabolism and can be targeted using bioactive peptides. Polypeptide medicines conceived and developed for targeted intervention in signaling pathways are meant to give improved options for treating linked clinical disorders based on this understanding [8].
Malignant growth conclusion includes the different strategies and methods used to recognize or affirm the presence of disease. Finding normally includes an assessment of the patient’s history, clinical assessments, survey of research facility test results and radiological information, and minute assessment of tissue tests got by biopsy or fine-needle aspiration. The illness at the beginning phase, when it has a high potential for a fix [9]. Intercessions are accessible which allows the early identification and successful treatment of around 33% of cases.
The early discovery suggests the determination of disease at a beginning phase in its turn of events and is in this way for the most part expected to bring about enhancements intolerant results utilizing traditional treatment procedures. Screening is a term regularly utilized for approaches that encourage early malignant growth recognition. Screening innovations must be fit for distinguishing little tumors at the beginning phase. Critically, they ought to recognize tumors at a phase when they can be restored by medical procedure alone or when they are more receptive to treatment, subsequently improving patient mortality and bleakness.
Some are the systems which contribute to the analysis of malignant growth
Discovery of Novel Molecular Markers for Early Detection
Novel Germ-Line Markers of Risk
Tissue-Specific Markers of Early Carcinogenesis and carcinogenesis Risk
Serum Mark
Circulating Tumor and Other Cells
Novel Molecular Imaging Approaches
4.1 Molecular (sub-atomic) diagnosis of cancer
Sub-atomic analysis reveals the various changes that happen during the change of an ordinary cell to a tumor cell and catches this data as articulation designs. Mechanically printed microarrays, Real-time PCR, and mi RNAs are generally utilized procedures for estimating this articulation example and help analysts to separate between a typical and a diseased cell. Sub-atomic conclusion through proteomics utilizes surface improved laser desorption/ionization season of flight mass spectrometry and peptide receptors in the planning of protein designs that are associated with harmful development. Nanoscale gadgets quantum spots and carbon nano-cylinders can be promising nano-instruments for compelling estimation of danger. Every one of these methods offers an extraordinary guarantee for altering the finding of disease [10].
4.1.1 Malignant growth diagnosis and nanotechnology
Malignant growth nanotechnology is an interdisciplinary territory of examination which covers a tremendous and various cluster of gadgets like nano-vectors for the focused on the conveyance of anticancer medications and imaging contrast specialists. Nanotechnology is a developing science that can be effectively utilized for malignant growth conclusions in the future. Nanotechnology has developed with wide applications for sub-atomic imaging, sub-atomic determination, and focused on the treatment of malignancy. It assumes a significant function in understanding the objective of identifying changing cell populaces right on time by in vivo imaging or ex vivo investigation. This permits the suitable mix of operators to be picked (in light of exact natural data on the tumor), focusing of these specialists (while keeping away from organic hindrances) to the early disease sores to dispose of or contain them without security impacts on sound tissue, and observing the treatment impact progressively [10].
The essential justification associated with disease nanotechnology is that nano-meter-sized particles, for example, semiconductor quantum specks and iron oxide nanocrystals, have optical, attractive, or basic properties that are not accessible from atoms or mass solids. At the point when connected with tumor focusing on ligands, for example, monoclonal antibodies, peptides, or little atoms, these nanoparticles can be utilized to target tumor antigens (biomarkers) just as tumor vasculatures with high fondness and particularity [10]. In the size scope of 5–100 nm breadth, nanoparticles additionally have huge surface regions and utilitarian gatherings for forming to different indicative (e.g., optical, radioisotopic, or attractive) and helpful (e.g., anticancer) specialists. With negligible malignancy cell test readiness, substrate authoritative to even a few antibodies creates a quantifiable change in the gadget’s conductivity, prompting a 100-overlap increment in affectability over current indicative methods.
Nanoscale cantilevers, minute, adaptable pillars taking after a column of plunging sheets, are fabricated utilizing semiconductor lithographic strategies. These can be covered with atoms fit for restricting explicit substrates-DNA corresponding to a particular quality grouping, for instance. Such micron-sized gadgets, involving numerous nanometer-sized cantilevers, can recognize single atoms of DNA or protein. Quantum dabs, nanoscale gems of a semiconductor material, for example, cadmium selenide, are another promising nanoscale instrument for research center diagnostics. Nanowires and nano cantilever exhibits are among the main methodologies a work in progress for the early discovery of precancerous and threatening injuries from organic liquids [10, 11].
These improvements raise energizing open doors for customized oncology in which hereditary and protein biomarkers are utilized to analyze and treat malignant growth dependent on the atomic profiles of individual patients [11].
Nanotechnology is a quickly extending field, including the advancement of man-made materials in the 5–200 nanometer size range. This measurement tremendously surpasses that of standard natural particles, yet it’s lower run moves toward that of numerous proteins and organic macromolecules. In the logical world, the expression “nano” is, nonetheless, to some degree uncertain since it does not assign similar reality for physicists, scientific expert and researcher [12].
Nanorechnology as a rule and nanoparticles specifically have upset the organization of medication. It includes the designing of utilitarian framework at the sub-atomic scale. Such framework are described by remarkable physical, optical and electronic highlights that are appealing for diciplines going from materials science to biomedicine. By ideals of their exceptional physicochemical properties, nanoparticles have indicated guarantee in conveying a scope of particles to wanted destinations in the body. To create more secure and more compelling remedial nanoparticles, analyst have planned novel multifunctional nanoparticle stage for cell/tissue-explicit focusing on, continued or set off medication conveyance, co-conveyance of synergistic medication blend [13].
Nanotechnology is a promising logical way to deal with production, design and manufacture materials, for example, nanoparticles whose size extents between 1 and 1000 nm scale. Their minuscule size, huge surface territory to volume proportion and potential to functionalize their surface give nanoparticles phenomenal physico-concoction properties for their different applications. Nanoparticles have been widely investigated for analytic and remedial applications in clinical and drug industry to fix infections, for example, malignant growth [14].
The essential objectives for examination of nano-bio-innovations in drug conveyance include:
More specific drug focusing on and conveyance
Reduction in harmfulness while keeping up restorative impacts
Greater security and biocompatibility
Faster improvement of new safe prescriptions
Nanoparticles stacked with the helpful medication can be moved to infection site for focused medication conveyance utilizing following strategies: [15].
Active targeting
Passive targeting
Physical targeting
Active targeting: it includes adjusting the nanoparticle surface by restricting ligands, for example, antibodies and proteins onto the outside of nanoparticle so as to build their take-up by target site. Little size, morphology and electrochemical properties of nanoparticles impact the improved penetration maintenance impact, consequently expanding the capacity of tumor cells to assimilate the nanoparticles contrasted with the ordinary cells. Thus the nanoparticles can be latently focused to the site [15, 16].
Passive targeting: EPR effect became a golden standard in the design of passive tumor-targeted systems. This effect is mostly depends on intrinsic tumor biology and in particular (1) the rate of angiogenesis and lymphangiogenesis, (2) the degree of perivascular tumor growth and the density of the stromal response and, (3) pressure inside the tumor. All the mentioned factors provides a physicochemical characteristic of nanocarriers which will determine its drug delivery efficiency [15, 16].
Physical targeting: Utilizes outside upgrades to direct the nanoparticle to the objective site. The outer boosts additionally control the medication discharge measure. For instance, in the event of photo-thermal treatment light is utilized while in attractive hyperthermia treatment, attractive field is utilized to manage the nanoparticles to the objective site [16].
The drug is either covalently bonded to or physically entrapped in the polymer matrix, depending on the technique of manufacture of polymeric-based drug carriers [17]. The resultant products might be capsules (polymeric nanoparticles or polymer–drug conjugates), polymeric micelles with an amphiphilic core/shell, or hyper-branched macromolecules.
Albumin, chitosan, and heparin are all naturally occurring polymers that have been utilized to carry DNA, oligonucleotides, and proteins, as well as medicines. Recently, serum albumin has been employed as a carrier in the creation of paclitaxel nanoparticles [nanometer-sized albumin-bound paclitaxel, which has been used in the clinic to treat metastatic breast cancer] [18].
Polyamidoamine dendrimer, which was conjugated with cisplatin, is the most extensively employed dendrimer as a scaffold [18]. Dendrimers’ highly changeable surface allows them to be conjugated with many molecules at once, such as imaging contrast agents, targeting ligands, or therapeutic medicines, resulting in a dendrimer-based multifunctional drug delivery system [19].
6. Special emphasis on mesoporous silica nanoparticles
Various nanodevices have been accounted like carbon nanotubes, quantum specks, and polymeric micelles, and so on in the field of nanotechnology. In the current situation, mesoporous nanoparticles are developing for their notable medication convey and focusing on purposes. Verifiably, Kresge et al. have portrayed a method for joining sol–gel chemistry with liquid crystal line templating to develop ordered porous molecular sieves characterized by periodic arrangements of uniformly sized mesopores (distance across between 2 nm and 50 nm) consolidated inside an indistinct silica matrix. Mesoporous silica nanoparticles (MSNs) have gotten obvious as a promising and novel medication delivery agent because of their one-of-a-kind mesoporous structure that saving a degree of synthetic solidness, surface usefulness and biocompatibility guarantee the controlled delivery, and target drug delivery of an assortment of API particles [20]. Mesoporous silica materials were found in 1992 by the Mobile Oil Corporation have gotten extensive consideration because of their boss literary properties like, high surface territory, enormous pore volume, tuneable pore diameter, and tuneable pore size distribution. Low toxicity and high loading limit of drug make Mesoporous silica nanoparticles, superior in utilization for controlled and target drug delivery. Essentially, silica is broadly present in nature in contrast with other metal oxides like titanium and iron oxides it has nearly better biocompatibility. The mesoporous type of silica has one-of-a-kind properties, especially in loading of drug, nanoparticles at high amounts, and in the resulting delivery. Because of solid Si-O bond, silica-based mesoporous nanoparticles are steadier to outside reaction, for example, degradation and mechanical stress when contrasted with niosomes, liposomes, and dendrimers which restrain the need of any outer adjustment in the amalgamation of MSNs (Figures 1 and 2) (Table 2) [25, 26].
Figure 1.
Schematic representation of synthesis of MSNs.
Figure 2.
Indicates different diagnostic techniques for cancer using MSNs.
6.1 Biocompatibility, biodegradability, toxicity and safety of MSNPs
To be useful for biomedical purposes, any nanomaterial must qualify for regulatory criteria about its biosafety without toxicity. Reasonable evidence on the in vivo toxicity assessment of nanomaterials in animal and human models is needed in this context. Criticality is specifically related to the toxicity and clearance of the MSNs with regard to size, shape, porosity, surface area and charge and chemical functionality. Two scientists, Lin and Haynes, analyzed the impact of various particle sizes of MSNPs varying from 25 to 225 nm by hemolysis testing of red blood cells (RBCs), which revealed a higher percentage of haemolysis found in smaller particle sizes of MSNPs in comparison to larger particles presumably due to the higher surface area [4, 27]. It has been stated in the literature that MSU-2 and MCM-41 are biocompatible when tested against non-cancer CHO cell line model [28]. The toxicological profiles of bare/native MSNPs on animal models were also tested by some investigators and high susceptibility was observed on reticuloendothelial systems, rendering them undesirable for intravenous administration by coupling with therapeutic agents [29]. Furthermore, the toxicity mitigation was attempted by conjugating the MSNPs with lipid matrices, which eventually demonstrated a substantial reduction in the toxicity of MCF-7 cells with regard to noncoated MSNPs after 48 h of incubation time [30]. The analysis of haemolysis also revealed relatively safe characteristics of the lipid-coated MSNPs over the uncoated ones. Recently, literature research on the production of PEG-coated organic-inorganic hybrid silica nano system (HMONs) reported substantially improved biodegradability and biocompatibility properties. The in vivo cytotoxicity assessment of the developed HMONs also did not disclose any significant pathophysiological improvements in the main organs (heart, liver, spleen, lung and kidney), which also verified in vivo biocompatibility of the PEG-conjugated HMONs [31].
6.2 Multidisciplinary nature of Mesoporous silica
Mesoporous Silica as Biosensor: The surface to volume ratio of NPs is very high, which enables ample functional ligands to be integrated and also allows multivalence on the surface of NP, which strengthens interactions with targets. MSN derivatives are often capped and gated in order to manipulate their applications in Controlled-release systems (CRS). In order to build different biosensors, various detection technologies were combined with the CRS [2, 32, 33].
Mesoporous Silica as Solubility Enhancer: The solubility enhancement mechanism of the mesoporous silica is clearly associated with the conversion of unstable crystalline form to stable amorphous form. Mesoporous silica has proved to be advantageous for poorly soluble drugs in increasing its solubility. MSNs have a high specific surface area, high pore volume and appropriate pore sizes in the molecular range, ordered pore structures and silanol groups on their surfaces that can interact with a variety of drug molecules. It also protects drug from external environment [34, 35].
Mesoporous Silica as wound healing aid: Mesoporous silica has found its application in this field as well. Nanoparticles have the ability to glue together the tissues by nano bridging effect. Nanobridging requires a particle size less than 100 nm while the clotting of blood depends on the porosity and the particle size of MSNs [36, 37].
The main explanation behind the simple alteration of silica nanoparticles is silanol groups. With abundant and commercially available silane reagents, these groups can react. Then Silanes add other functional groups to the silica nanoparticles surface. The most commonly utilized silanes, along with different alkylsilane, PEG-silanes, have amine or sulfur groups at the end. Amine or thiol-ended groups give a simple linking chemistry with widely used molecules such as functionalized N-hydroxysuccinide (NHS), isothiocyanates, maleimides etc. [38, 39]. It is also possible to use each of these functional groups to tune the surface charge of the silica nanoparticles [40, 41]. Alkylsilanes are used for the treatment of hydrophobic surfaces and for increasing the echogenicity of silica nanoparticles. PEG-silanes graft PEG onto silica nanoparticles, increase the durability of the particles in biological fluids and extend the circulation period in vivo [42, 43]. Below Table 3 presents the most commonly used silanes and their purposes for nanoparticle surface modification.
Methods Employed for Surface Functionalization of MSNPs.
Methods employed for surface functionalization of MSNPs are shown below
Co-Condensation
Multifunctionalization
Grafting
Co-condensation process (one-pot synthesis)
The direct condensation of organosilanes with a combination of silica precursors and surfactant templates is co-condensation. The process of co-condensation provides the probability of providing homogeneously dispersed organic groups without pore-blockage or shrinkage problems on the complete inner pore surfaces [56]. Also, the morphology of MSNPs can be regulated by the incorporation of various organosilanes. Researchers also observed that organosilanes with hydrophobic groups interact with surfactant hydrophobic tails, allowing the organic groups of organosilanes to be intercalated with the surfactant micelles [57, 58]. This leads to long cylindrical micelles being stabilized, and MSNPs are obtained in rod shapes. Hydrophilic organosilanes, on the contrary, do not interfere with surfactants and no further micelle stabilization exists, creating spherical particles with spontaneously directed pore structures. In binding with surfactant molecules, functional groups with a greater capacity to compete with silicate anions will be more likely to occur on MSNP surfaces than those weakly binding functional groups that are normally embedded in the silica frameworks and are thus unavailable [59].
Grafting method (Post-Synthesis Modification)
Grafting modifies a prefabricated inorganic mesoporous NP surface by adding functional groups to the material surface, typically after elimination of surfactants, and is thus a form of post-synthesis. The surface silanol groups (Si- OH) of MSNPs, typically present in high concentrations, serve as adequate anchoring points for organic functionalization in this process. Silylation is often achieved through surface functionalization of organic groups by grafting. The process of silylation takes place on free (≡Si─OH) and geminal silanol (=Si(OH)2) groups. Hydrogen-bonded silanol groups, however, form hydrophilic networks and functionalization is carried out to a small degree. Functionalization is conducted on the outer surface and at the opening of the pores of MSNPs in the grafting process. The drawback of grafting is the inhomogeneity in the coverage of surfaces because silanols are kinetically more accessible on the outside surface and at the opening of the mesopores than those located in the inner pore walls. Organosilane grafted MSNPs have better preserved pore structures as compared to co-condensed MSNPs and are more thermally stable. In most cases, due to the small amount of free surface silanol groups, the degree of functionalization by the grafting process is lower than that of the co-condensation method [59].
Multifunctionalization
It is beneficial to be able to combine more than one form of functional group with the MSNPs in order to create a more complex MSNP-based DDS. It is possible to co-condense two different organosilanes with silica precursors, but different silane hydrolysis rates will weaken the ordering of MSNPs and reduce the quantity of loading. In addition, the positions of the functional groups cannot be strictly controlled. Therefore, for the selective integration of functional groups into the external and internal surface of MSNPs, the multifunctionalization approach was developed using both cocondensation and grafting methods. The MSNPs are first synthesized using the cocondensation method in this step, and the free groups of silanols are then functionalized in a supercritical fluid medium using the grafting method. The surfactant is then extracted in this synthesis with the extraction of alcohol acid, resulting in the forming of the mesoporous structure [59].
Nanoparticles serving as both diagnostic and therapeutic agents are theranostic and multimodal imageable nanoparticles. Theranostic nanoparticles are useful instruments for the detection and selection of patients followed by supportive care. The benefits of various imaging modalities are combined by multimodal nanoparticle contrast agents. The toxicity of nanoparticles that contain harmful components such as heavy metals can also be minimized by silica. Another useful technique for making multifunctional nanoparticles is doping functional elements such as lanthanide ions into silica. Gadolinium (Gd), for example, is a widely used MRI T1 contrast agent but it is toxic due to its concentration in tissues such as the liver, bone, and kidneys. Gadolinium-doped silica nanoparticles not only increase the contrast of the MRI but also decrease the toxicity of Gd (Figure 3) [60].
Figure 3.
Theranostic application of mesoporous silica.
Rieter et al. attached a silylated Gd complex paramagnetic monolayer to a Luminescent [Ru(2,2′-bypyridine)3] Cl2 with reverse microemulsion core by a water-in - oil process. Due to the [Ru(2,2′-bypyridine)3] Cl2 centre and the Gd in the silica cap, this nanoparticle supplies fluorescent and MRI signals. Also, silica is conjugated with diethylenetriaminetetraacetate (DTTA), which generates seven binding sites for Gd3+ ions to reduce nanoparticles’ toxicity due to Gd3+ core leaching. The nanoparticle is tiny enough (< 50 nm) to be endocytized by monocyte cells, which enables cells to be imaged multimodally in vitro. This nanoparticle is used by the investigators as target-specific contrast agents for optical and magnetic resonance imaging (MR) of rheumatoid arthritis in mice [61].
Photoacoustic (PA) imaging combining optical and ultrasound benefits have been developed to enhance diagnosis accuracy and sensitivity for early stage tumors, which offers the best resolution in deep tissue relative to some traditional imaging methods [62]. Thus, PA imaging, conveniently paired with ultrasound imaging, will greatly increase clinical diagnosis in the integrated method [63]. To this end, a conjugate of hyaluronate-silica nanoparticle (HA – SiNP) was synthesized by Lee and colleagues as a PA contrast agent: An MSNs-based liver targeting therapy. The PA amplitude in the liver after HA-SiNP conjugate injection was dramatically improved by 95.9 percent relative to standard liver over other PA contrast agents due to the powerful photoacoustic signal of SiNP in NIR windows, which offers more anatomical and functional information for HCC diagnosis [64].
As an activatable theranostic agent, Suk Ho Hong and associates developed an Indocyanine green-loaded hollow mesoporous silica nanoparticle. They became highly fluorescent once the nanoparticles reached the cancer cells through endocytosis. The study was carried out using cellular uptake quantitative analysis, in vitro cytotoxicity and in vitro phototoxicity research. The substance has shown significant potential for selective fluorescent NIR cancer [65]. Pegah Khosravian and Folic acid/methionine processed and tested, functionalizes mesoporous silica nanoparticles for docetaxel distribution. Usage of 3-aminopropyl triethoxy silane to achieve amine functionalisation. In vivo and ex vivo fluorescence imaging, In vivo application of nanoparticles, infrared and spectroscopy test MSNs, MTT assay, SEM, TEM. With small size distribution, the synthesized MSN-NH2 exhibited an average diameter of 49 nm. MSNs with a narrow size distribution, functionalized and DTX-loaded [66]. Hartono and colleagues 2016, prepared a system for curcumin bioavailability enhancement; which was intended for oral use. It possessed cubic shaped MSNs. It possessed better release profile and a higher solubility. Physical characterization was carried out by using TEM, XRD, FTIR, In-vitro release studies. Higher bioavailability of MSN-A-Cur and MSM-A-Cur was observed when compared to that of free curcumin. Pore size of 1.8 nm was observed in amine functionalized MCM-41 [67].
N. Lashgari and associates in 2016 demonstrated that as solid chemosensors and various advanced hybrid materials modified by fluorescence molecules have recently been prepared, the organic–inorganic hybrid nanomaterials have major advantages. In the other hand, mesoporous silica’s homogeneous porosity and wide surface area make it a promising inorganic help [68].
Pande Vishal and colleagues 2018, mesoporous silica nanoparticles are produced as a targeted therapy medium that serves as a carrier for gemcitabine hydrochloride with fluorescein loaded onto nanoparticles for fluorescence microscopy tracing and imaging. As a target for pancreatic cancer cells, folic acid is conjugated with mesoporous silica nanoparticles [69]. Pande Vishal et al. 2020 produced a Targeted & Theranostic DDS using MSNs, fluorescein and magnetic nanoparticles. The therapeutic agent used in this system was gemcitabine hydrochloride. The folic acid functionalisation to the MSNs guided it to the cancer cells while the fluorescein and magnetic nanoparticles can be traced with the help of suitable technique and played the role of diagnostic agents in the system. The system showed excellent invitro anticancer activity and superior in vivo bioavailability was found in case of MSNs as compared to plain drug [70].
A flexible of mesoporous silica is engineered by Zang& colleagues in 2019 and worked on the basis of aqueous well-dispersed, including ion doping, surface alteration and pore adsorption. Thus, by endowing certain specific materials, a multifunctional theranostic nanoplatform is obtained. Gd ions are added to mesoporous silica (GM nanoparticles) in depth via a co-assembly process, which is used as the primary MRI carrier. In addition, the hyaluronic acid (HA) molecule surface graft leads to lymph system-targeted distribution (GMH nanoparticles). In addition, the development of Iopamidol (IGMH nanoparticles) and DOX (DGMH nanoparticles) functional molecules could integrate diagnosis and treatment with CT and sustained drug release. They present evidence that IGMH and DGMH nanoparticles are strongly active in vitro and in vivo for the lymphatic system, emphasizing CT and MR imaging of IGMH nanoparticles in the lymphatic system and chemotherapy and MR imaging of DGMH nanoparticles in lymphatic cancer [71]. Nihal Elbialy et al. 2019, Synthesized smart theranostic Platform of PEGylated mesoporous silica nanoparticles loaded-curcumin for the prevention and treatment of cancer. This Nanocarrier increased Bioavailability of Curcumin as well as provided a self-Fluorescent System for bioimaging of cancer [72].
In this review we have discussed different types of cancer & its therapies. We have specially emphasized on Mesoporous silica, its functionalisation and its use as Theranostic Medicine. Mesoporous silica with different diagnostic agents facilitated drug delivery to targeted site and at cellular level. Different diagnostic aids help its tracing. Various external stimuli may lead its path toward the target site or may be opted by the functionalisation done on the surface. While preclinical trials of MSNs have been successfully performed, there are currently no MSNs approved to be used in clinics. There are some crucial problems for MSNs that need to be resolved. First, the latest small animal models are not sufficient to test the delivery efficacy and long-term toxicity of nanoparticles in humans. Secondly, the production of MSNs on the laboratory scale cannot easily be replicated on the industrial scale of production for clinical use, especially in the case of complex modified MSNs. Third, there is no rigorous appraisal criteria that may confused the researchers to enhance the current MSNs. These problems when solved can lead to a potential formulation development based on MSNs for cancer Theranostic.
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Written By
Ajinkya Pote, Vikas Ahirrao and Vishal Pande
Submitted: 20 April 2022Reviewed: 17 May 2022Published: 18 July 2022
Open access peer-reviewed chapter
