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

Theranostics. 2019 Feb 14;9(5):1358-1368. doi: 10.7150/thno.32106. eCollection 2019.

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: cancer therapy; drug release; logic-gated; modular nanomedicine; nanovesicle.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Drug Liberation*
  • Drug Therapy / methods*
  • Humans
  • Mice, Nude
  • Molecular Targeted Therapy / methods
  • Nanomedicine / methods*
  • Nanostructures / administration & dosage
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents