Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy

Hongtong Lu; Shasha He; Qingfei Zhang; Xiaoyuan Li; Zhigang Xie; Zigui Wang; Yanxin Qi; Yubin Huang

doi:10.1039/D1BM01154E

Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy†

Hongtong Lu,^ab Shasha He,^a Qingfei Zhang,^ab Xiaoyuan Li,^c Zhigang Xie,

^ab Zigui Wang,*^d Yanxin Qi*^a and Yubin Huang

*^ac

Author affiliations

* Corresponding authors

^a State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
E-mail: yxqi@ciac.ac.cn, huangyb350@nenu.edu.cn

^b University of Science and Technology of China, Hefei 230026, P. R. China

^c Faculty of Chemistry, Northeast Normal University, Changchun 130024, P.R. China

^d Zhengzhou Immunobiotech Co., Ltd, Zhengzhou 450016, P.R. China
E-mail: wangzigui@autobio.com.cn

Abstract

The clinical application of conventional chemotherapeutic agents, represented by cisplatin, is limited by severe side effects. So, it is essential to explore more safer and controlled drug delivery systems for synergistic chemotherapy. In this work, we designed dual-sensitive dual-prodrug nanoparticles (DDNPs) for photoactivated platinum-based synergistic chemotherapy. With photosensitivity, DDNPs could be photoactivated from inert Pt(IV) to toxic Pt(II) under safe UVA light in a spatiotemporally controlled manner. Concurrently, mild Image ID:d1bm01154e-t1.gif could be generated from DDNPs to assist the endo/lysosomal escape of DDNPs for better photoactivated chemotherapy (PACT). Furthermore, with acid-sensitivity, demethylcantharidin (DMC), a protein phosphatase 2A (PP2A) inhibitor, was released to block the DNA repair pathway and thereby could sensitize platinum-based chemotherapy in intracellular acidic microenvironments. Along with a precise ratio (Pt : DMC = 1 : 2), DDNPs had a powerful synergistic anti-cancer effect in vitro and in vivo. In the future, DDNPs have great potential as a safe and multifunctional drug delivery system for precise nanomedicine in clinical treatments.

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DOI: https://doi.org/10.1039/D1BM01154E
Article type: Paper
Submitted: 22 Jul 2021
Accepted: 29 Aug 2021
First published: 31 Aug 2021

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Biomater. Sci., 2021,9, 7115-7123

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Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy

H. Lu, S. He, Q. Zhang, X. Li, Z. Xie, Z. Wang, Y. Qi and Y. Huang, Biomater. Sci., 2021, 9, 7115 DOI: 10.1039/D1BM01154E

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Biomaterials Science

Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy†

Abstract

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Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy

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