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Research Article | Open Access

Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

Ruo-Lin Jiang1,6,§Hui-Na Liu1,§Yu-Fan Yang1Zhi-Cheng Zhang2Qi Dai1,2Xiao-Yan Bao1Lin-Jie Wu1Ya-Xin Qin1Xin Tan1Xiao-Yan Sun1Xu-Fang Ying1,6Zhi-Qing Ben1Min Han1,2,3,4,5()
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310058, China
Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, China
Jinhua Institute of Zhejiang University, Jinhua 321299, China
National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China
Polytechnic institute, Zhejiang University, Hangzhou 310015, China

§ Ruo-Lin Jiang and Hui-Na Liu contributed equally to this work.

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In this study, we prepared a zwitterionic hyaluronic acid carrier HA-spermine/trimethylcystamine/DOX-TPP (HSTD) and co-deliver nucleic acid drugs and chemotherapy drugs, in order to improve the transfection efficiency of siRNA and endow it with the synergistic killing effect of chemotherapy drugs.

Abstract

Traditionally, hyaluronic acid has been widely used for drug delivery, but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative, which makes it difficult to carry hydrophobic drugs and small interfering RNA (siRNA) with the same charge. Based on previous studies, we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP (HSTD) for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic interaction. Then, N,N,N-trimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA, thus promoting transfection. Moreover, when co-delivered with the chemotherapy drug doxorubicin (DOX), this novel nanocarrier showed promising synergy in inhibiting tumor growth.

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Nano Research
Article number: 94907076
Cite this article:
Jiang R-L, Liu H-N, Yang Y-F, et al. Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment. Nano Research, 2025, 18(1): 94907076. https://doi.org/10.26599/NR.2025.94907076
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