Engineering of a universal polymeric nanoparticle platform to optimize the PEG density for photodynamic therapy

Nanocarrier-mediated photodynamic therapy (PDT) has attracted extensive attention due to its locoregional therapeutic effect, minimal toxicity to normal tissues, and activation of immune system capability. However, it is still unclear how the physico-chemical properties of nanocarriers affect their PDT therapeutic efficacies, which could be very different from those for chemotherapy. Herein, to demonstrate the effect of PEG density on PDT efficacy, we synthesized a series of random polyphosphoesters (PPEs) with different PEG contents by regulating the molar ratios of these monomers, and then these PPEs were used to prepare chlorin e6 (Ce6)-loaded polymeric nanoparticles with tunable PEG density. Thereafter, the PDT efficacies of these nanoparticles were carefully and comprehensively evaluated. We demonstrate that the moderate PEG density (3.01 PEG/nm) of nanocarrier exhibited the best PDT therapeutic efficacy in a mouse model of pancreatic cancer due to its efficient balance of prolonged circulation and tumor cellular uptake.