Advances in cell-penetrating poly(disulfide)s for intracellular delivery of therapeutics.

Yu Wan, Wangxia Wang, Qiuyue Lai, Mingyu Wu, Shun Feng

Journal: Drug discovery today 2023;28(8):103668

PMID: 37321318

Full Text on Elsevier Science View on PubMed

Abstract

Efficient intracellular delivery is essential for most therapeutic agents; however, existing delivery vectors face a dilemma between efficiency and toxicity, and always encounter the challenge of endolysosomal trapping. The cell-penetrating poly(disulfide) (CPD) is an effective tool for intracellular delivery, as it is taken up through thiol-mediated cellular uptake, thus avoiding endolysosomal entrapment and ensuring efficient cytosolic availability. Upon cellular uptake, CPD undergoes reductive depolymerization by glutathione inside cells and has minimal cytotoxicity. This review summarizes CPD's chemical synthesis approaches, cellular uptake mechanism, and recent advances in the intracellular delivery of proteins, antibodies, nucleic acids, and other nanoparticles. Overall, CPD is a promising candidate carrier for efficient intracellular delivery.

Address: Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: [email protected].; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

DOI: 10.1016/j.drudis.2023.103668

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MeSH Terms: Disulfides, Proteins, Nanoparticles, Antibodies, Biological Transport, Cell-Penetrating Peptides