Compared to their bulk materials, nanomaterials offer a wide range of distinct physicochemical properties that are ideal for many biomedical purposes. Some of the different applications of nanomaterials within medicine include drug delivery, tissue engineering, bio-micromechanical systems (bioMEMS), biosensors, microfluidics, and diagnostics. Of these, nanomaterial-based drug delivery systems have emerged as one of the primary uses of nanotechnology within medicine.
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The small size of nanomaterials is mainly responsible for their various advantageous properties. For drug delivery systems, nanomaterials have not only improved the targeting specificity of these drugs but have also improved circulation time, biodistribution, solubility, intracellular delivery, and ability to cross biological membranes. For cancer treatment purposes, nanocarriers have also been found to allow for drugs to accumulate at high levels at the tumor site.
An Overview of Inorganic Nanomaterials
Inorganic nanoparticles (INPs) have been widely studied over the past several decades for a wide variety of industrial purposes. Within the field of biomedicine, INPs have been utilized for both diagnostic and therapeutic purposes.
For example, gold nanoparticles (AuNPs) have been widely studied due to their biocompatibility and the ease of controlling their size distribution and shape, which can include spheres, nanorods, and cubes, among others. Furthermore, the surface chemistry of AuNPs can also be easily modified through conjugation with various polymers, antibodies, small-molecule therapeutics, and molecular probes.
Another prevalent type of INP includes iron oxide nanoparticles (IONPs), which have been widely used since the 1960s for diagnostic imaging and therapeutic purposes. To date, the United States Food and Drug Administration (FDA) has approved several IONPs for both therapeutic and imaging use. In particular, magnetite (Fe3O4) nanoparticles have been used as a contrast agent for magnetic resonance imaging (MRI) due to their extremely low cytotoxicity profile, magnetic responsiveness, tunability, and controlled size and surface modification.
One type of silica nanoparticle (SiNP) that has emerged as an interesting alternative approach to drug delivery is mesoporous silica nanoparticles (MSNPs). MSNPs are unique due to their nanopores that can be used to encapsulate hydrophobic drugs for efficient delivery. Furthermore, these nanopores can be modulated through the use of various templates, surfactant concentrations, pH, and solvents during their synthesis.
MSNPs have also been studied for their use as stimuli-responsive drug release systems. In this application, the surface of MSNPs can be manipulated to adjust the controlled release of the encapsulated drug after a trigger reaction occurs. Some of the different medications that have been incorporated into MSNP-based drug delivery systems include vancomycin and adenosine triphosphate (ATP).
An Overview of Organic Nanomaterials
Several organic-based nanomaterials, including liposomes, micelles, and polymer nanoparticles, have been developed for drug delivery purposes.
Liposomes, for example, or a type of lipid-based nanomaterial that consists of an aqueous core surrounded by a phospholipid bilayer. This structure is therefore amphiphilic and allows for the formation of a thermodynamically stabilized vesicle. Some of the most common types of phospholipids that are often incorporated into liposomes include phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylglycerol. In addition to these phospholipids, stabilizers like cholesterol are also often incorporated into a liposome to increase their stability.
As drug delivery vehicles, liposomes have been shown to improve the permeation of hydrophilic drugs, protect peptides and other protein-based drugs against harsh conditions like the stomach's acidity, improve the bioavailability of drugs, as well as reduce toxicity and adverse side effects. Notably, the targeting ability and rate of drug release of liposomes depend on the type of lipid incorporated into the liposome and their size, lamellarity, and surface properties.
Applications in Cancer Treatment
Both INPs and organic nanoparticles have been widely studied for their use as drug delivery vehicles for anticancer drugs. For example, AuNPs and IONPs and their combination have been explored for HER2 receptor-based targeting of drugs for the treatment of breast cancer.
Several other HER2-based targeting treatments have been developed based on modified nanocarriers to improve the therapeutic efficacy of specific antineoplastic agents. For example, one recent study discussed the development of trastuzumab conjugated pH-sensitive double-emulsion nanocapsules (DENCs) that are stabilized by both poly (vinyl alcohol) and magnetic nanoparticles. In this work, the researchers used these nanocarriers for the co-delivery of doxorubicin (DOX) and paclitaxel, which were found to improve the targeting ability of these drugs towards HER2 positive breast cancer cells.
The first FDA-approved nanodrug was Doxil®, which is a PEGylated liposomal DOX formulation that passively targets tumors via the enhanced permeability and retention (EPR) effect. Importantly, Doxil® is associated with significantly reduced cardiotoxicity as compared to when DOX is used alone.
Challenges
Despite the numerous advantages associated with both INPs and organic nanoparticles as drug delivery vehicles, several major challenges still account for their limited clinical use. One of the most significant issues includes the regulatory mechanisms currently in place for nanomedicines and the safety and toxicity assessments that need to be better tailored for nanomedical applications.
Continue reading: Manifesting Multidisciplinary Nanomedicine Research with the MMS.
References
Hassan, S., Prakash, G., Orzturk, A. B., et al. (2017) Evolution and clinical translation of drug delivery nanomaterials. Nanotoday 15; 91-106. Available at: doi:10.1016/j.nanotod.2017.06.008.
Dutta, B., Barick, K. C., & Hassan, P. A. (2021) Recent advances in active targeting of nanomaterials for anticancer drug delivery. Advances in Colloid and Interface Science 296. Available at: doi:10.1016/j.cis.2021.102509.
Patra, J. K., Das, G., Fraceto, L. F., et al. (2018) Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology 16(71). Available at:doi:10.1186/s12951-018-0392-8.
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