Reversibly cross-linked polyplexes enable cancer-targeted gene delivery via self-promoted DNA release and self-diminished toxicity

Biomacromolecules
Hua HeLichen Yin

Abstract

Polycations often suffer from the irreconcilable inconsistency between transfection efficiency and toxicity. Polymers with high molecular weight (MW) and cationic charge feature potent gene delivery capabilities, while in the meantime suffer from strong chemotoxicity, restricted intracellular DNA release, and low stability in vivo. To address these critical challenges, we herein developed pH-responsive, reversibly cross-linked, polyetheleneimine (PEI)-based polyplexes coated with hyaluronic acid (HA) for the effective and targeted gene delivery to cancer cells. Low-MW PEI was cross-linked with the ketal-containing linker, and the obtained high-MW analogue afforded potent gene delivery capabilities during transfection, while rapidly degraded into low-MW segments upon acid treatment in the endosomes, which promoted intracellular DNA release and reduced material toxicity. HA coating of the polyplexes shielded the surface positive charges to enhance their stability under physiological condition and simultaneously reduced the toxicity. Additionally, HA coating allowed active targeting to cancer cells to potentiate the transfection efficiencies in cancer cells in vitro and in vivo. This study therefore provides an effective approach ...Continue Reading

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Citations

Oct 26, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Lalita B RaneAnupa A Kumbhar
Apr 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qiang LiuZhi-Gang Zhao
Jun 28, 2017·ACS Applied Materials & Interfaces·Lipeng ZhuLichen Yin
Jun 29, 2017·ACS Applied Materials & Interfaces·Fangfang LiLichen Yin
Mar 16, 2017·Topics in Current Chemistry·Hu-Lin JiangChong-Su Cho
Feb 28, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Qian LiWencheng Zhang
Aug 22, 2017·Frontiers in Pharmacology·Xiaotian ZhaoWeien Yuan
Jul 14, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Saisai WangYiyun Cheng
May 4, 2021·Chemical Reviews·Ramya KumarTheresa M Reineke
Jun 13, 2016·ACS Biomaterials Science & Engineering·Hong-Yin WangFu-Gen Wu
May 21, 2015·ACS Applied Materials & Interfaces·Yan-Yu YangDe-Cheng Wu
Mar 3, 2018·ACS Applied Materials & Interfaces·Chunhui RuanChen Jiang

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