Commentary: Nanoparticle-Based Chemotherapy Delivery and Potential Health Risks: Prospects for Effective Clinical Translation

Abstract

With recent advancements, chemotherapy is one of the most prevalent regimens for cancer treatment. However, the heterogeneity of tumor biology and healthy cell-damaging potential of chemotherapy remain challenges. As a solution, nanoparticle-based delivery is advancing. Besides its promising potential, effective clinical translation and commercialization of nanoparticle-based chemotherapy should get attention to ensure the absence of potential health risks. Specifically, the permeability potential of nanoparticles across biological barriers can lead to drug accumulation in vital organs and produce harm. Therefore, for effective design and clinical application of next-generation nanomedicine, pharmaceutical formulation scientists should conduct intensive studies. They involve studying the properties of drug-loaded nanoparticles in the microenvironment of the target site and the impact of interspecies differences using quantitative and mechanistic studies. It creates a comprehensive understanding of the specific properties of nanoparticles and their interaction potential with biological systems. This commentary justifies the requirement for comprehensive knowledge of the above-mentioned criteria and tests for the success of nanomedicine for chemotherapy delivery.

Background

Cancer is one of the leading causes of death worldwide. It accounted for nearly 10 million deaths in 2020. Commonly, breast, lung, colon, rectum, and prostate cancers are the most prevalent.^1,2 In addition to its rapid prevalence and metastasis, the heterogeneity of tumor biology and challenges of successful therapy using conventional therapies become significant barriers to increasing the life expectancy of patients. Among the available cancer treatment methods, chemotherapy remains one of the most prevalent regimens. However, its frequency of administration, inadequate tumor-selective potential, and severe toxicity remain the causes of patient discomfort and treatment failure. Therefore, their cytotoxicity to both neoplastic and normal cells may cause permanent damage to vital organs such as the heart, lungs, liver, kidneys, reproductive system, or others. These challenges have attracted the application of nanotechnology to improve its success and sidestep impacts on patient survival.^3-6

The upcoming application of nanotechnology in medicine and healthcare (nanomedicine) has gained popularity. Predominantly, its potential in drug delivery and medical diagnosis has notable hope to prevent and treat severe conditions such as cancer. However, successful design and clinical translation of nanomedicine requires substantial advancement in understanding the physicochemical and biological properties of nanoparticles and nanomedicine itself. They include their potential to modulate the integrity of physiological barriers, exploit transport systems on the endothelium or epithelial cell layers, and enhance uptake. Through this, nanomedicine overcomes limitations associated with conventional drug delivery systems, such as the bioavailability and overexpression of drug efflux transporters.^7-9 Therefore, pharmaceutical formulation scientists should conduct intensive studies for effective clinical translation of nanoparticle-based delivery systems and commercialization globally.

The design and development of a nanoparticle-based chemotherapy delivery system requires consideration of its potential to conquer multiple biological barriers. They include blood circulation, cellular uptake, drug release rate, penetration, and accumulation in the tumor. These potentials can lead to the association of drug-loaded nanoparticles with ligands, following the endogenous transport processes and passing through biological barriers. However, they can penetrate through off-targeted membranes of vital organs such as the blood-brain, blood-testes, blood-follicle, placental, blood-bile, and glomerular filtration. Finally, the drug molecules are released and distributed into these organs, where they interact with cellular materials. With the normal cell-damaging potential of most chemotherapeutic agents, it may end up with potential health risks such as genotoxicity, teratogenicity, cytotoxicity, neurotoxicity, hepatotoxicity, local tolerance, and other side effects.^6,10-15

Therefore, the side effects of chemotherapeutic agents, incomprehensive knowledge of nanoparticles’ specific properties, and their interaction with biological systems open up new potential risks to vital organs. These challenges become the bottleneck to the promising clinical use and commercialization of nanoparticle-based chemotherapy. Therefore, they should attract the special attention of the scientific community.

Future Prospects for Effective Clinical Translation and Commercialization

Besides the health revolution driven by nanomedicine, clinical translation should not avoid potential health risks. Hence, during nanoparticle-based delivery design and development, their potential toxicity to healthy, nontargeted tissue in clinical use needs attention. Particularly for drugs with a narrow therapeutic index, such as chemotherapy, an in-depth understanding of nanoparticle interactions with biological systems, such as their translocation across biological barriers, is critical. Moreover, intensive quantitative and mechanistic studies and considering interspecies differences in nanoparticulate performance need special attention. Therefore, while designing next-generation nanoparticle-based chemotherapy, comprehensive knowledge of the unique biological interaction potential of nanoparticles and conditions in the microenvironment of the target site can facilitate the rapid realization of great promise for the future.