1. A Logic-Gated Modular Nanovesicle Enables Programmable Drug Release for On-Demand Chemotherapy
- Author
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Zhantong Wang, Mingru Zhang, Zijian Zhou, Ying Ma, Gang Niu, Xianzhong Zhang, Longguang Tang, Xiaoyuan Chen, Rui Tian, Zhen Yang, Lixin Lang, Shoujun Zhu, Wenpei Fan, and Dale O. Kiesewetter
- Subjects
Fluorescence-lifetime imaging microscopy ,Biodistribution ,Mice, Nude ,Medicine (miscellaneous) ,Antineoplastic Agents ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,nanovesicle ,01 natural sciences ,modular nanomedicine ,Drug Delivery Systems ,Drug Therapy ,In vivo ,Cell Line, Tumor ,Animals ,Humans ,Molecular Targeted Therapy ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,drug release ,Edman degradation ,Chemistry ,Prodrug ,021001 nanoscience & nanotechnology ,Xenograft Model Antitumor Assays ,Nanostructures ,0104 chemical sciences ,Drug Liberation ,Nanomedicine ,Treatment Outcome ,cancer therapy ,logic-gated ,0210 nano-technology ,Linker ,AND gate ,Research Paper - 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.
- Published
- 2019