Redox-Responsive Polymeric Nanoparticle for Nucleic Acid Delivery and Cancer Therapy: Progress, Opportunities, and Challenges

Cancer development and progression of cancer are closely associated with the activation of oncogenes and loss of tumor suppressor genes. Nucleic acid drugs (e.g., siRNA, mRNA, and DNA) are widely used for cancer therapy due to their specific ability to regulate the expression of any cancer-associated genes. However, nucleic acid drugs are negatively charged biomacromolecules that are susceptible to serum nucleases and cannot cross cell membrane. Therefore, specific delivery tools are required to facilitate the intracellular delivery of nucleic acid drugs. In the past few decades, a variety of nanoparticles (NPs) are designed and developed for nucleic acid delivery and cancer therapy. In particular, the polymeric NPs in response to the abnormal redox status in cancer cells have garnered much more attention as their potential in redox-triggered nanostructure dissociation and rapid intracellular release of nucleic acid drugs. In this review, the important genes or signaling pathways regulating the abnormal redox status in cancer cells are briefly introduced and the recent development of redox-responsive NPs for nucleic acid delivery and cancer therapy is systemically summarized. The future development of NPs-mediated nucleic acid delivery and their challenges in clinical translation are also discussed. Redox-responsive polymeric nanoparticles (NPs) are widely used for nucleic acid drug delivery and cancer therapy. Herein, the important signaling pathways regulating tumor redox status are summarized and the recent development of redox-responsive NPs for nucleic acid delivery and cancer therapy is systemically reviewed. The future development of NPs-mediated nucleic acid delivery and their challenges in clinical translation are also discussed.image

Automated summary

Cancer development and progression are closely linked to the activation of oncogenes and loss of tumor suppressor genes. Nucleic acid drugs, such as siRNA, mRNA, and DNA, have been widely used for cancer therapy due to their ability to regulate the expression of cancer-associated genes. However, the negatively charged nature of nucleic acid drugs makes them susceptible to degradation and limits their ability to enter cells. To overcome this, specific delivery tools, such as nanoparticles, have been developed. In this review, the authors summarize the important genes and signaling pathways involved in the abnormal redox status of cancer cells, and discuss the recent development of redox-responsive nanoparticles for nucleic acid delivery and cancer therapy. The challenges and future development of nanoparticle-mediated nucleic acid delivery are also discussed.