Zwitterionic-to-cationic charge conversion polyprodrug nanomedicine for enhanced drug delivery

Sheng Wang^1,✉, Fuwu Zhang³, Guocan Yu³, Zhantong Wang³, Orit Jacobson³, Ying Ma³, Rui Tian³, Hongzhang Deng³, Weijing Yang³, Zhi-Yi Chen^2,✉, Xiaoyuan Chen^3,✉

1. School of Life Sciences, Tianjin University and Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin 300072, China
2. Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, The Liwan Hospital of the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, China
3. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States

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Citation:
Wang S, Zhang F, Yu G, Wang Z, Jacobson O, Ma Y, Tian R, Deng H, Yang W, Chen ZY, Chen X. Zwitterionic-to-cationic charge conversion polyprodrug nanomedicine for enhanced drug delivery. Theranostics 2020; 10(15):6629-6637. doi:10.7150/thno.47849. Available from https://www.thno.org/v10p6629.htm

Abstract

Zwitterionic surface modification is a promising strategy for nanomedicines to achieve prolonged circulation time and thus effective tumor accumulation. However, zwitterion modified nanoparticles suffer from reduced cellular internalization efficiency.

Methods: A polyprodrug-based nanomedicine with zwitterionic-to-cationic charge conversion ability (denoted as ZTC-NMs) was developed for enhanced chemotherapeutic drug delivery. The polyprodrug consists of pH-responsive poly(carboxybetaine)-like zwitterionic segment and glutathione-responsive camptothecin prodrug segment.

Results: The ZTC-NMs combine the advantages of zwitterionic surface and polyprodrug. Compared with conventional zwitterionic surface, the ZTC-NMs can respond to tumor microenvironment and realize ZTC surface charge conversion, thus improve cellular internalization efficiency of the nanomedicines.

Conclusions: This ZTC method offers a strategy to promote the drug delivery efficiency and therapeutic efficacy, which is promising for the development of cancer nanomedicines.

Keywords: charge conversion, zwitterionic, polyprodrug, triggered drug release, nanomedicine