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Polyphosphoestered Nanomedicines with Tunable Surface Hydrophilicity for Cancer Drug Delivery.

The surface hydrophilicity of nanoparticles has a major impact on their biological fates. Ascertaining the correlation between nanoparticles surface hydrophilicity and their biological behaviors is particularly instructive for future nanomedicines design and their antitumor efficacy optimization. Herein, we designed a series of polymeric nanoparticles based on polyphosphoesters with well controlled surface hydrophilicity in molecular level and systemically evaluated their biological behaviors. The results demonstrated that high surface hydrophilicity preferred lower protein absorption, better stability, longer blood circulation as well as higher tumor accumulation but lower cellular uptake. Upon encapsulation of drugs, nanoparticles with high hydrophilicity showed excellent anti-tumor therapeutic efficacy in both primary and metastatic tumors as compared to the relatively hydrophobic ones. Further analyses revealed that the superior antitumor outcome was attributed to the balance of tumor accumulation and cellular uptake, demonstrating the particular importance of nanoparticles surface hydrophilicity regulation on antitumor efficacy. Our work provides a potent guideline for rational designation on surface hydrophilicity of nanoparticles for cancer treatment optimization.