The surface hydrophilicity of nanoparticles has a major impact on their biological fates. Ascertaining the correlation between nanoparticle surface hydrophilicity and their biological behaviors is particularly instructive for future nanomedicine design and their antitumor efficacy optimization. Herein, we designed a series of polymeric nanoparticles based on polyphosphoesters with well-controlled surface hydrophilicity in the molecular level and systemically evaluated their biological behaviors. The results demonstrated that high surface hydrophilicity preferred lower protein absorption, better stability, longer blood circulation, and higher tumor accumulation but lower cellular uptake. Upon encapsulation of drugs, nanoparticles with high hydrophilicity showed an excellent antitumor 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 nanoparticle surface hydrophilicity regulation on the antitumor efficacy. Our work provides a potent guideline for a rational designation on the surface hydrophilicity of nanoparticles for cancer treatment optimization.

中文翻译：

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具有可调表面亲水性的多磷酸酯化纳米药物，用于癌症药物的递送。

纳米颗粒的表面亲水性对其生物命运有重大影响。确定纳米颗粒表面亲水性与其生物学行为之间的相关性对未来的纳米药物设计及其抗肿瘤功效的优化特别具有指导意义。在这里，我们设计了一系列基于聚磷酸酯的聚合物纳米颗粒，这些分子在分子水平上具有良好的表面亲水性，并系统地评估了它们的生物学行为。结果表明，高表面亲水性优选较低的蛋白质吸收，更好的稳定性，更长的血液循环和更高的肿瘤蓄积，但更低的细胞摄取。封装药物后，与相对疏水的相比，具有高亲水性的纳米颗粒在原发性和转移性肿瘤中均表现出优异的抗肿瘤治疗效果。进一步的分析表明，优异的抗肿瘤结果归因于肿瘤积累和细胞摄取的平衡，这表明纳米颗粒表面亲水性调节对抗肿瘤功效的特别重要性。我们的工作为合理指定纳米粒子的表面亲水性以优化癌症治疗提供了有效的指导。证明了纳米颗粒表面亲水性调节对抗肿瘤功效的特别重要性。我们的工作为合理指定纳米粒子的表面亲水性以优化癌症治疗提供了有效的指导。证明了纳米颗粒表面亲水性调节对抗肿瘤功效的特别重要性。我们的工作为合理指定纳米粒子的表面亲水性以优化癌症治疗提供了有效的指导。