مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Engineering Exosomes for Cancer Therapy
Engineering Exosomes for Cancer Therapy
Seyed Hossein Khaleghinejad,1,*
1. Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran
Introduction: Abstract
Exosomes are tiny vesicles that naturally transport molecules between cells and have emerged as promising systems for cancer therapy. Due to their ability to deliver drugs, proteins, and microRNAs(miRNA), they offer a selective, stable alternative to traditional cancer treatments, which often have severe side effects. Exosomes can be engineered to target cancer cells more effectively, reducing tumor growth and enhancing immune responses. However, challenges like production efficiency and standardization still need to be overcome. Artificial exosomes, which combine the benefits of natural and synthetic systems, are being developed to meet these needs. Future research could further improve exosome-based therapies, particularly for cancer treatment.
Introduction
Exosomes are tiny extracellular vesicles that transport biological molecules such as proteins, microRNAs, and metabolites. Despite their small size and low biomolecule expression, their biological function has only been recently understood. Nevertheless, exosomes have quickly emerged as promising systems for drug delivery, particularly in cancer therapy. Current antitumor drugs often cause severe side effects, underscoring the need for more selective and stable delivery methods(1, 2). Exosomes, whether naturally sourced or synthetically engineered, offer a versatile platform for loading different types of molecules, including small compounds and therapeutic agents. Moreover, exosomes can be customized by selecting specific source cells or engineering them with affinity tags, allowing better adaptation to the complex tumor microenvironment(3).
Innovative cancer treatments are urgently needed to address metastatic cancer, which causes more than 8 million deaths annually worldwide. Exosomes, which are naturally absorbed by cells, can efficiently deliver drugs, therapeutic proteins, and microRNAs. As our knowledge of exosome formation, release, and uptake grows, interest in using these vesicles as targeted delivery systems for cancer therapies has also risen(4). Exosome engineering allows for control over their contents and migration paths, showing potential in cancer treatment. Studies using both viral and non-viral methods have engineered parent cells to produce modified exosomes or altered exosome content after secretion. The results have been promising, demonstrating reduced tumor cell migration and proliferation, improved immune responses, increased cancer cell death, and heightened sensitivity to chemotherapy. However, to fully realize the potential of exosomes in clinical applications, standards for their production, isolation, and characterization must be established(5).
Methods: Basic Properties of Exosomes
Exosomes are a subset of extracellular vesicles (EVs), which are nanosized, membrane-bound structures secreted by cells. EVs contain proteins, lipids, and nucleic acids specific to their cell of origin and can be categorized into exosomes, apoptotic bodies, and microvesicles(6). Exosomes are produced through the endocytic pathway and are typically 40–100 nm in diameter, with a lipid bilayer containing a variety of proteins, such as heat shock proteins (HSPs), tumor-related genes, and fusion proteins(7). They also carry nucleic acids, including messenger RNA (mRNA), microRNAs (miRNA), and noncoding RNAs, which help regulate gene expression and may play a role in cancer progression. Exosomes facilitate intercellular communication by transferring these molecules between cells, which has made them an attractive option for drug delivery (Figure 1) (8).
Exosomes are produced by various cell types and are present in numerous bodily fluids. Mesenchymal stem cell-derived exosomes, which lack certain immune markers, are especially promising for therapeutic applications due to their ability to evade immune detection(9).
Results: Drug Delivery Vehicles for Cancer Therapy
Cancer is the second leading cause of death worldwide. Conventional treatments such as chemotherapy have significant side effects, largely due to their non-selective nature, harming healthy tissues along with cancer cells. Therefore, developing drug delivery systems (DDS) that more specifically target cancer cells is crucial cancer(10, 11). Nanotechnology has advanced cancer treatment by creating drug carriers that accumulate in tumors while minimizing toxicity(12, 13). However, challenges such as toxicity and poor biocompatibility remain. Exosomes, as natural DDS, provide an innovative alternative, offering advantages such as immune evasion and efficient cellular entry. Exosomes have also gained attention as drug carriers due to their role in intercellular communication(14-16).
Artificial Exosomes as a Drug Delivery Vehicle
To overcome the challenges of natural exosome production and standardization, artificial exosomes have been developed. These artificial vesicles, created using nanobiotechnology, combine natural and synthetic nanoparticles' benefits and show potential for drug delivery applications. Despite these advancements, hurdles such as large-scale production and drug loading remain(17-19).
Engineering Exosomes for Drug Delivery
Exosomes have advantages over synthetic systems, including their ability to fuse with cell membranes, improving drug delivery. Strategies to target exosomes to tumors include using peptides or antibodies to bind specific receptors on cancer cells. However, avoiding rapid clearance by the immune system remains a challenge. Modifying exosomes to bypass immune detection or using metalloproteinases to alter exosome contents are potential solutions(20-22).
Conclusion: Summary and Future Perspective
Exosomes offer significant advantages as drug delivery systems, with low immunogenicity, high safety, and minimal cytotoxicity. However, challenges such as standardization, drug loading, and large-scale production need to be addressed for their full potential to be realized. Artificial exosomes could offer scalable solutions, and future developments in this area could revolutionize cancer treatment(23-25).