Accidental discoveries have always led to intriguing research in science, and one such incident by a group of researchers has been published in the journal American Chemical Society.
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Polymeric nanoparticles have so far been proven to be useful for biomedical applications such as for the fabrication of nanostructures; however, their natural function for biological activities has not received much attention. This article will uncover the natural disposition of polymeric nanoparticles for function in biological activities such as targeting submandibular salivary glands.
The Challenge of Drug Targeting in Tissues
A major challenge within drug delivery and nanomedicine consist of the ability to target specific tissues.
While there have been increased efforts in this area by innovative researchers through enhancing the selectivity of current nanomedicine drug delivery systems as well as novel strategies to increase targeting, this challenge has not yet been overcome.
The field of nanomedicine thus far has attempted to target specific tissues by utilizing ligands to identify and recognize receptors located on tissue-specific cells. This has resulted in ligands such as antibodies, peptides, aptamers, and others being conjugated onto nanoparticle surfaces, allowing functionalization and increasing the specificity of drug delivery systems. Still, with complex designs, there is difficulty translating a ready-made product for clinical use.
Achieving Tissue Targeting
The use of unmodified nanoparticles with intrinsic biological activities could be potentially used to decrease the level of processing required for a fully functional and functionalized drug delivery system. This has made biological macromolecules such as peptides, nucleic acids, and proteins desirable due to their natural ability to have specific molecular interactions with tissues.
Additionally, synthetic polymers can also be exploited for this purpose. They also possess the ability to have interactions for targeting biological functions due to moieties that selectively interact with targets to interfere with their operations.
However, with polymeric nanoparticles being widely used as a drug carrier in nanomedical research, the use of these specialized particles would be useful for the purpose of tissue targeting.
Researchers within this particular study found that polyethylenimine–poly(lactic-co-glycolic acid)2 (PEI–PLGA), usually used in gene and protein delivery, can mediate the targeting of submandibular salivary glands of mice after being intravenously injected for in vivo experimentation.
The research team found that unmodified polyethylenimine–poly(lactic-co-glycolic acid)2 (PEI–PLGA) nanoparticles with the hydrophilic PEI fully exposed on the surface around the aqueous phase could selectively accumulate in these mice submandibular salivary glands due to a high affinity with acetylcholine receptors in the specific tissue.
This is comparable to FDA-approved drugs such as muscarinic acetylcholine receptor subtype 3 (M3 receptor)-binding drugs. This illustrates the potential similarity in efficacy, a promising step for a novel drug system utilizing nanomedicine in the form of polymeric nanoparticles for gene targeting.
PEI–PLGA nanoparticles can adsorb many negatively charged biological molecules such as RNA, protein, and DNA and have already been commonly utilized for the delivery of nucleic acid or protein drugs through nonselective static electric attraction.
However, the novel aspect of this particular research focused on PEI-PLGA nanoparticles being able to interact with the M3 acetylcholine receptor, which is expressed in a large volume in the submandibular salivary glands.
The development of synthetic polymers such as PEI-PLGA nanoparticles for biological applications can illustrate the interaction of polymers and proteins and can aid in the development of design strategies for nanomedical drug systems.
Additionally, this research would be useful for the development of M3 receptor-targeted therapies to enhance the treatment of diseases relating to the expression of the M3 receptor. An example of such a disorder includes Sjögren syndrome (SS) , an autoimmune disease that affects exocrine glands, including salivary and lacrimal glands.
This receptor is also overexpressed in other organs such as the brain, with cholinergic transmission at muscarinic acetylcholine receptors being critical for higher brain function, including learning and memory and a loss of synapses resulting in symptoms relating to Alzheimer’s disease.
However, while this potential for brain treatment for motor neuron diseases can be technically possible, further research is required as few PEI-PLGA nanoparticles have been observed in the brain, which may be due to the blood-brain barrier.
The researchers have theorized that other muscarinic receptor subtypes such as M1 receptors are also overexpressed in the submandibular gland, so improving the selectivity of PEI-PLGA to target these subtypes can also be a research point.
While no obvious change was found in the level of salivary secretion within mice injected with PEI-PLGA nanoparticles within 24 hours, the targeting ability of these novel polymeric nanoparticles for biological activities is a promising start for possible interference in M3 signaling pathways and function.
This research can be exploited for many useful applications as summarized above and further illustrates the significance of nanomedicine in advancing diseases.
Continue reading: Green Synthesis of Ag Nanoparticles for Antibacterial Applications.
Further Reading and References
Haam, J. and Yakel, J., (2017) Cholinergic modulation of the hippocampal region and memory function. Journal of Neurochemistry, 142, pp.111-121. Available at: https://doi.org/10.1111/jnc.14052
Heller Brown, J. and Laiken, N., (2012) Acetylcholine and Muscarinic Receptors. Primer on the Autonomic Nervous System, pp.75-78. Available at: https://doi.org/10.1016/B978-0-12-386525-0.00015-9
Xu, J., Wan, K., Wang, H., Shi, X., Wang, J., Zhong, Y., Gao, C., Zhang, Y. and Nie, G., (2021) Polyethylenimine–Poly(lactic-co-glycolic acid)2 Nanoparticles Show an Innate Targeting Ability to the Submandibular Salivary Gland via the Muscarinic 3 Receptor. ACS Central Science, 7(11), pp.1938-1948. Available at: https://doi.org/10.1021/acscentsci.1c01083