“…Although some porphyrin-based hydrophobic photosensitizers were approved as PDT drugs for clinical use, the PDT outcome is often compromised by the inherent hydrophobicity, insufficient tumor accumulation, tumor hypoxia, and adverse effects due to nonspecific accumulation in skin, liver, spleen, and so forth . Therefore, various inorganic and organic nanomaterials including metallic nanoparticles, carbon-based materials, and cyanine dye-related nanomaterials were fabricated for enhanced PDT. − However, most of the above nanoparticles accumulate in the reticuloendothelial system (RES) such as liver and spleen, resulting in slow and inefficient clearance of nanoparticles and leading to the potential toxicity of trapped nanomaterials in RES. − Given the glomerular capillary cutoff diameter of 10 nm, ultrasmall nanoparticles with a diameter less than 10 nm could be rapidly excreted through kidney. − In addition, smaller particle size is an appealing feature for deeper and more uniform delivery of nanomaterials in tumors. However, the size of sub-10 nm also results in reduced efficacy of passive targeting through the enhanced permeability and retention (EPR) effect in tumors.…”