Size-Switchable Nanoparticles with Self-Destructive and Tumor Penetration Characteristics for Site-Specific Phototherapy of Cancer

The normoxic and hypoxic microenvironments in solid tumors cause cancer cells to show different sensitivities to various treatments. Therefore, it is essential to develop different therapeutic modalities based on tumor microenvironment. In this study, we designed size-switchable nanoparticles with self‐destruction and tumor penetration characteristics for site-specific phototherapy of cancer. This was achieved by photodynamic therapy (PDT) in the perivascular normoxic microenvironment due to high local oxygen concentrations and photothermal therapy (PTT) in the hypoxic microenvironment that are not in proximity to blood vessels due to a lack of effective approaches for heat transfer. In brief, a poly(amidoamine) dendrimer with photothermal agent indocyanine green (PAMAM-ICG) was conjugated to the amphiphilic polymer through a singlet oxygen-responsive thioketal linker and then loaded with photosensitizer chlorin e6 (Ce6) to construct a nanotherapy platform (denoted as SNPICG/Ce6). After intravenous inject...