DOI: 10.1002/mabi.202300238 ISSN:

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

Lei Xu, Yuan Cao, Ya Xu, Rong Li, Xiaoding Xu
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials
  • Bioengineering
  • Biotechnology


Cancer development and progression of cancer is closely associated with the activation of oncogenes and loss of tumor suppressor genes. Nucleic acid drugs (e.g., siRNA, mRNA, and DNA) have been 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 could not 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) have been 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, we briefly introduce the important genes or signaling pathways regulating the abnormal redox status in cancer cells and systemically summarize the recent development of redox‐responsive NPs for nucleic acid delivery and cancer therapy. We also discuss the future development of NPs‐mediated nucleic acid delivery and their challenges in clinical translation.

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