Recent advances in exosome-mediated nucleic acid delivery for cancer therapy

Abstract

Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs. Graphical Abstract

Mesenchymal stem cell-derived exosomes as new tools for delivery of miRNAs in the treatment of cancer

“…Additionally, they are destroyed after entering the body. Therefore, exosomes can serve as excellent carriers for miRNAs ( Zhang et al, 2022 ). There are two methods for miRNA enrichment/loading in exosomes.…”

Mechanism underlying circRNA dysregulation in the TME of digestive system cancer

“…In digestive system cancers, circRNAs with carcinogenic effects are usually expressed stably in cancer cells, but they can also be encapsulated by tiny vesicles in exosomes to deliver some vital biological information from the interior of tumor cells and affect the expression of downstream miRNAs, thus affecting the progression of related cancers ( 282 , 283 ). For example, circ-100338 derived from HCC cell lines can be transferred to adjacent cells by exosomes and promote the proliferation and angiogenesis of surrounding HUVECs, as well as the invasion and metastasis of HCC cells ( 284 ).…”

Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma

“…They are very important for information transmission between cells. Studies have shown that exosomes have cell selectivity and tissue specificity and can accurately transport “goods” from parental cells to recipient cells [ 156 , 157 ]. In the future, researchers may be able to load miRNAs that enhance the radiotherapy sensitivity of NPC cells into exosomes so that NPC cells can uptake these miRNAs and overexpress them, enhancing therapeutic effects in patients with radiation resistance.…”