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

Photodynamic therapy (PDT) is a promising approach tocancer treatment,but the heterogeneity of the tumor microenvironment (TME) limits itsapplication. Tumor vasculature is thought to be involved in abnormalTME. Therefore, tumor vascular normalization (TVN) is expected tobe a strategy to reshape TME. We prepared a graded-release nanodrugcombining TVN and PDT, named as PEVM, with the core of lipid nanoparticlesfor sustained release of anti-angiogenic drugs and the shell of apH-sensitive polymer linked to a photosensitizer, and evaluated itstherapeutic effect on a breast cancer model. We found that PEVM couldachieve mutual benefits in both therapeutic effects. TVN not onlyincreased the intratumoral oxygen level as a raw material for PDT,but also activated the anti-tumor immune response, further improvingthe efficacy of PDT. PEVM showed favorable anti-tumor efficiency andexhibited the potential of combining TVN and PDT.