Polyphosphoestered Nanomedicines with Tunable Surface Hydrophilicity for Cancer Drug Delivery
Polyphosphoestered Nanomedicines with Tunable Surface Hydrophilicity for Cancer Drug Delivery
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具有可调表面亲水性的多磷酸酯纳米药物用于癌症药物输送
DOI：
10.1021/acsami.0c07016
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yu-Cai Wang
中科院分区：
文献类型：
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作者：
Li Wang;Shu-Ya Li;Wei Jiang;Hao Liu;Jia-Xiang Dou;Xiao-Qiu Li;Yu-Cai Wang
纳米粒子的表面亲水性对其生物学命运有着重要影响。确定纳米粒子表面亲水性与其生物学行为之间的相关性对于未来的纳米药物设计和抗肿瘤功效优化具有特别的指导意义。在此，我们设计了一系列基于聚磷酸酯的聚合物纳米颗粒，在分子水平上具有良好的表面亲水性控制，并系统地评价了它们的生物学行为。结果表明，高表面亲水性有利于降低蛋白质吸收，更好的稳定性，更长的血液循环，和更高的肿瘤积累，但更低的细胞摄取。在药物包封后，与相对疏水的纳米颗粒相比，具有高亲水性的纳米颗粒在原发性和转移性肿瘤中显示出优异的抗肿瘤治疗效果。进一步的分析显示，上级抗肿瘤结果归因于肿瘤积聚和细胞摄取的平衡，证明纳米颗粒表面亲水性调节对抗肿瘤功效的特别重要性。我们的工作提供了一个强有力的指导原则，合理设计的表面亲水性纳米粒子的癌症治疗优化。
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.