Adv Healthc Mater. 2024 Jan 22:e2302333. doi: 10.1002/adhm.202302333. Online ahead of print.

ABSTRACT

In recent years, anticancer effects of disulfiram, a clinical drug for anti-alcoholism, have been confirmed. However, several defects limit clinical translation of disulfiram obviously, such as Cu(II)-dependent anticancer activity, instability and non-selectivity for cancer cells. Herein, a phosphate and hydrogen peroxide dual-responsive nanoplatform (PCu-HA-DQ) is reported, which is constructed by encapsulating disulfiram prodrug (DQ) and modifying hyaluronic acid (HA) on copper doping metal-organic frameworks (PCu MOFs). PCu-HA-DQ is expected to accumulate in tumor by targeting CD-44 receptors and enable guidance with magnetic resonance imaging. Inside the tumor, Cu(DTC)₂ will be generated in situ based on a dual-responsive reaction. In detail, the high concentration of phosphate could induce the release of DQ, after that, the intracellular hydrogen peroxide would further mediate the generation of Cu(DTC)₂ . In vitro and in vivo results indicate PCu-HA-DQ could induce the apoptosis as well as immunogenic cell death (ICD) of tumor cells distinctly, leading to enhanced immune checkpoint inhibitor (ICI) efficacy by combining the anti-programmed death-1 antibody. This work provides a portable strategy to construct dual-responsive nanoplatform integrating tumor-targeted ability and multi-therapy, and the designed nanoplatform is also an ICD inducer, which presents prospect for boosting systemic antitumor immunity and ICI efficacy. This article is protected by copyright. All rights reserved.

PMID:38253350 | DOI:10.1002/adhm.202302333