Polymer-Modified Lipid Nanoparticles with Microenvironment-Responsive Graded Release for Amplified Photodynamic Therapy Through Tumor Vascular Normalization

Photodynamic therapy (PDT) is a promising approach to cancer treatment, but the heterogeneity of the tumor microenvironment (TME) limits its application. Tumor vasculature is thought to be involved in abnormal TME. Therefore, tumor vascular normalization (TVN) is expected to be a strategy to reshape TME. We prepared a graded-release nanodrug combining TVN and PDT, named as PEVM, with the core of lipid nanoparticles for sustained release of anti-angiogenic drugs and the shell of a pH-sensitive polymer linked to a photosensitizer, and evaluated its therapeutic effect on a breast cancer model. We found that PEVM could achieve mutual benefits in both therapeutic effects. TVN not only increased the intratumoral oxygen level as a raw material for PDT, but also activated the anti-tumor immune response, further improving the efficacy of PDT. PEVM showed favorable anti-tumor efficiency and exhibited the potential of combining TVN and PDT.