Engineering of a universal polymeric nanoparticle platform to optimize the PEG density for photodynamic therapy
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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/nm2) 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.
KeywordsPEG density photodynamic therapy polymeric nanoparticles biological effect cancer therapy
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This work was supported by the National Natural Science Foundation of China (51822302, 51773067, 31870993), National Key R&D Program of China (2017YFA0205601), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2017B030306002), the Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2017ZT07S054), Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110102001), and the Fundamental Research Funds for the Central Universities.