粘液穿透和细胞结合多两性离子胶束作为用于癌症药物递送的有效口服纳米药物,Advanced Materials

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粘液穿透和细胞结合多两性离子胶束作为用于癌症药物递送的有效口服纳米药物
Advanced Materials ( IF 27.4 ) Pub Date : 2022-02-23 , DOI: 10.1002/adma.202109189
Wufa Fan _{1,

2,

3,

4} , Qiuyu Wei _{2,

3,

4} , Jiajia Xiang _{2,

3,

4} , Yisi Tang _{2,

3,

4} , Quan Zhou _{2,

3} , Yu Geng _{2,

3} , Yanpeng Liu ₄ , Rui Sun _{2,

3} , Lei Xu ₄ , Guowei Wang ₄ , Ying Piao _{2,

3} , Shiqun Shao _{2,

3,

4} , Zhuxian Zhou _{2,

3,

4} , Jianbin Tang _{2,

3,

4} , Tao Xie _{2,

3} , Zichen Li ₁ , Youqing Shen _{2,

3,

4}

Affiliation

口服抗癌纳米药物因其易于和可重复的给药而非常受欢迎，但由于目前的纳米药物不能同时克服强大的粘液和绒毛屏障，因此生物利用度（BA）非常低，因此尚不可行。在此，这项工作提出了第一个能够快速渗透粘液和绒毛吸收并将紫杉醇 (PTX) 有效递送至肿瘤的聚合物胶束，其治疗效果甚至优于静脉内施用的基于聚乙二醇的对应物或游离 PTX。Poly[2-( N -oxide- N,N-diethylamino)ethyl methacrylate] (OPDEA) 是一种水溶性多两性离子，对蛋白质和其他生物大分子（如粘蛋白）具有高度的无污染性，但对磷脂的结合能力较弱。因此，其与聚（ε-己内酯）（OPDEA-PCL）的嵌段共聚物的胶束可以有效地渗透通过粘性粘液并与绒毛结合，从而触发转胞吞作用介导的跨上皮转运进入血液循环以实现肿瘤积累。口服胶束将 PTX 递送至肿瘤，有效抑制 HepG2 和患者来源的肝细胞癌异种移植物和三阴性乳腺肿瘤的生长。这些结果表明，基于 OPDEA 的胶束可以作为一种有效的口服纳米药物，用于递送其他小分子甚至大分子。

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Mucus Penetrating and Cell-Binding Polyzwitterionic Micelles as Potent Oral Nanomedicine for Cancer Drug Delivery

Orally administrable anticancer nanomedicines are highly desirable due to their easy and repeatable administration, but are not yet feasible because the current nanomedicine cannot simultaneously overcome the strong mucus and villi barriers and thus have very low bioavailability (BA). Herein, this work presents the first polymeric micelle capable of fast mucus permeation and villi absorption and delivering paclitaxel (PTX) efficiently to tumors with therapeutic efficacy even better than intravenously administered polyethylene glycol based counterpart or free PTX. Poly[2-(N-oxide-N,N-diethylamino)ethyl methacrylate] (OPDEA), a water-soluble polyzwitterion, is highly nonfouling to proteins and other biomacromolecules such as mucin but can weakly bind to phospholipids. Therefore, the micelle of its block copolymer with poly(ε-caprolactone) (OPDEA-PCL) can efficiently permeate through the viscous mucus and bind to villi, which triggers transcytosis-mediated transepithelial transport into blood circulation for tumor accumulation. The orally administered micelles deliver PTX to tumors, efficiently inhibiting the growth of HepG2 and patient-derived hepatocellular carcinoma xenografts and triple-negative breast tumors. These results demonstrate that OPDEA-based micelles may serve as an efficient oral nanomedicine for delivering other small molecules or even large molecules.

更新日期：2022-02-23

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