Functional Choline Phosphate Lipids for Enhanced Drug Delivery in Cancer Therapy,Chemistry of Materials

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Functional Choline Phosphate Lipids for Enhanced Drug Delivery in Cancer Therapy
Chemistry of Materials ( IF 7.2 ) Pub Date : 2021-01-05 , DOI: 10.1021/acs.chemmater.0c04443
Wenliang Wang ₁ , Sangni Jiang _{2,

3} , Shengran Li _{2,

3} , XinXin Yan _{2,

3} , Sanrong Liu ₂ , Xiaobo Mao ₁ , Xifei Yu _{2,

3}

Affiliation

Liposome formulations by zwitterionic lipids (e.g., phosphatidyl choline (PC)) have been widely applied in the clinical translation of nanomedicines. However, poor bioorthogonality in the PC lipid backbone and limited cellular uptake potency significantly impede the development of a therapeutic strategy. Herein, we synthesized a novel bioorthogonal zwitterionic lipid named choline phosphate (CP), with reversed PC charge orientation via a phospholane derivative ring-opening reaction. CP lipids can assemble into liposomes with excellent biocompatibility and stable physical and chemical properties similar to PC liposomes. Due to supramolecular ionic pair interactions with the cell membrane, doxorubicin (Dox)-loaded CP liposomes (CP-Dox) were preferentially taken up and accumulated in cells compared to PC-Dox, which significantly enhanced the cytotoxicity in cancer cells and inhibited tumor growth. Furthermore, we determined the bioorthogonality of the CP lipids by conjugating folate in situ using a “click” reaction, which showed specificity in targeting treatment for breast cancer. Our studies provide a new proof of concept that functional liposomes can be designed at the molecular level. We also expect that CP lipids may have potential in other applications, including biosensors, antifouling coatings, cell membrane mimetic engineering, and artificial cells.

中文翻译：

功能性胆碱磷酸脂可增强癌症治疗中的药物递送

由两性离子脂质（例如，磷脂酰胆碱（PC））制成的脂质体制剂已广泛应用于纳米药物的临床翻译中。但是，PC脂质主链的不良生物正交性和有限的细胞摄取能力显着阻碍了治疗策略的发展。在这里，我们合成了一种新型的生物正交性两性离子脂质，称为磷酸胆碱（CP），具有通过膦酸酯衍生物开环反应反向的PC电荷取向。CP脂质可以组装成脂质体，具有与PC脂质体相似的优异生物相容性和稳定的理化性质。由于超分子离子对与细胞膜的相互作用，与PC-Dox相比，阿霉素（Dox）负载的CP脂质体（CP-Dox）被优先吸收并积累在细胞中，显着增强癌细胞的细胞毒性并抑制肿瘤生长。此外，我们通过使用“点击”反应通过原位结合叶酸来确定CP脂质的生物正交性，该反应在乳腺癌的靶向治疗中显示出特异性。我们的研究提供了可以在分子水平上设计功能性脂质体的新概念证明。我们还期望CP脂质可能在其他应用中具有潜力，包括生物传感器，防污涂料，细胞膜模拟工程和人造细胞。我们的研究提供了可以在分子水平上设计功能性脂质体的新概念证明。我们还期望CP脂质可能在其他应用中具有潜力，包括生物传感器，防污涂料，细胞膜模拟工程和人造细胞。我们的研究提供了可以在分子水平上设计功能性脂质体的新概念证明。我们还期望CP脂质可能在其他应用中具有潜力，包括生物传感器，防污涂料，细胞膜模拟工程和人造细胞。

更新日期：2021-01-26

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