Theranostics 2019; 9(5):1358-1368. doi:10.7150/thno.32106

Research Paper

A Logic-Gated Modular Nanovesicle Enables Programmable Drug Release for On-Demand Chemotherapy

Longguang Tang1,2, Zhen Yang2, Zijian Zhou2✉, Ying Ma2, Dale O. Kiesewetter2, Zhantong Wang2, Wenpei Fan2, Shoujun Zhu2, Mingru Zhang2, Rui Tian2, Lixin Lang2, Gang Niu2, Xianzhong Zhang1✉, Xiaoyuan Chen2✉

1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA

Abstract

It remains a major challenge to achieve precise on-demand drug release. Here, we developed a modular nanomedicine integrated with logic-gated system enabling programmable drug release for on-demand chemotherapy.

Methods: We employed two different logical AND gates consisting of four interrelated moieties to construct the nanovesicles, denoted as v-A-CED2, containing oxidation-responsive nanovesicles (v), radical generators (A), and Edman linker conjugated prodrugs (CED2). The first AND logic gate is connected in parallel by mild hyperthermia (I) and acidic pH (II), which executes NIR laser triggered prodrug-to-drug transformation through Edman degradation. Meanwhile, the mild hyperthermia effect triggers alkyl radical generation (III) which contributes to internal oxidation and degradation of nanovesicles (IV). The second AND logic gate is therefore formed by the combination of I-IV to achieve programmable drug release by a single stimulus input NIR laser. The biodistribution of the nanovesicles was monitored by positron emission tomography (PET), photoacoustic, and fluorescence imaging.

Results: The developed modular nanovesicles exhibited high tumor accumulation and effective anticancer effects both in vitro and in vivo.

Conclusions: This study provides a novel paradigm of logic-gated programmable drug release system by a modular nanovesicle, which may shed light on innovation of anticancer agents and strategies.

Keywords: modular nanomedicine, logic-gated, nanovesicle, drug release, cancer therapy

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How to cite this article:
Tang L, Yang Z, Zhou Z, Ma Y, Kiesewetter DO, Wang Z, Fan W, Zhu S, Zhang M, Tian R, Lang L, Niu G, Zhang X, Chen X. A Logic-Gated Modular Nanovesicle Enables Programmable Drug Release for On-Demand Chemotherapy. Theranostics 2019; 9(5):1358-1368. doi:10.7150/thno.32106. Available from http://www.thno.org/v09p1358.htm