Transforming malignant tumors into vulnerable phenotypes via nanoscale coordination polymer mediated cell senescence and photodynamic therapy.

Abstract

Induction of senescence in cancer cells can thwart the proliferation of malignant tumors. Herein we report the design of AZT-P/pyro nanoscale coordination polymer particles consisting of 3-azido-2,3-dideoxythymidine monophosphate (AZT-P) in the core and photosensitizing pyro-lipid (pyro) in the shell for potent antitumor treatment. Gradual release of AZT-P in response to an acidic tumor microenvironment transforms cancer cells with unlimited proliferation capacity into senescent cells that are vulnerable to reactive oxygen species (ROS). Pyro selectively induces ROS generation and immunogenic cell death of cancer cells upon light irradiation. Co-delivery of AZT-P and pyro in a single particle prolongs their blood circulation times and enhances their accumulation in tumors. Additionally, the induction of senescence and ROS generation both contribute to the recruitment of immune cells to the tumors, resulting in an effective immune response to inhibit the growth of large subcutaneous tumors and metastatic spread of orthotopic tumors.