Bio-Inspired Amphoteric Polymer for Triggered-Release Drug Delivery on Breast Cancer Cells Based on Metal Coordination.
Bio-Inspired Amphoteric Polymer for Triggered-Release Drug Delivery on Breast Cancer Cells Based on Metal Coordination.
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DOI：
10.1021/acsami.1c03191
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发表时间：
2021-06-09
影响因子：
9.5
通讯作者：
Huang CJ
中科院分区：
文献类型：
--
作者：
Chen PC;Lai JJ;Huang CJ
纳米级配位聚合物是很有前景的抗癌药物递送载体，因为它们的表面组成和粒径可以调节，以利用增强的渗透和滞留效应，并且它们与金属阳离子的可逆相互作用能够在肿瘤部位触发药物释放。在此，我们利用二嵌段共聚物聚（2 - 甲基丙烯酰氧乙基磷酰胆碱） - 嵌段 - 聚（丙烯酸丝氨酸酯）（PMPC - b - PserA）开发了一种新型纳米级配位聚合物，并展示了其用于包封疏水性药物以及触发药物释放以在体外诱导乳腺癌细胞凋亡的用途。两性离子PMPC嵌段的灵感来源于细胞膜的抗污结构，PserA嵌段则源于蛋白质的两性氨基酸。该聚合物通过可逆加成 - 断裂链转移聚合反应合成，聚合物和氯化铁（FeCl₃）的混合物通过Fe³⁺与PserA的络合自组装成纳米粒子，亲水性的PMPC嵌段位于粒子表面。当Fe³⁺与丝氨酸（serA）的摩尔比为3∶1时，粒子的流体动力学直径为22.2纳米。姜黄素是一种天然的水不溶性多酚，用于增强化疗药物的效果，它作为水包油乳液被包封在粒子中，包封效率为99.6%，粒子载药量为32%。通过添加去铁胺（一种美国食品药品监督管理局批准的Fe³⁺螯合剂）实现姜黄素的触发释放；在较高的去铁胺浓度和较低的pH值下，姜黄素的释放效率提高。姜黄素的触发释放诱导了人三阴性乳腺癌细胞的凋亡；用载有姜黄素的纳米粒子和去铁胺处理24小时后，细胞存活率降至34.3%，而没有去铁胺触发药物释放时，细胞存活率>80%。这种纳米级配位聚合物的生物相容性、可调节的组成和尺寸、高疏水性药物载量以及触发释放能力使其非常适合用于抗癌药物递送。
Nanoscale coordination polymers are promising vehicles for anticancer drug delivery because their surface composition and particle size can be tuned to exploit the enhanced permeability and retention effect, and their reversible interaction with metal cations enables triggered drug release at the tumor site. Here we develop a novel nanoscale coordination polymer using the diblock copolymer poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(serinyl acrylate) (PMPC-b-PserA) and demonstrate its use for encapsulation of a hydrophobic drug and triggered drug release to induce breast cancer cell apoptosis in vitro. The zwitterionic PMPC block was inspired by the antifouling structure of cell membranes, and the PserA block by the amphoteric amino acids of proteins. The polymer was synthesized by reversible addition-fragmentation chain transfer polymerization, and a mixture of the polymer and FeCl3 self-assembled into nanoparticles via complexation of Fe3+ with PserA, with the hydrophilic PMPC block at the particle surface. At a 3:1 molar ratio of Fe3+ to serA, the hydrodynamic diameter of the particles was 22.2 nm. Curcumin, a natural water-insoluble polyphenol used to enhance the effects of chemotherapeutics, was encapsulated in the particles as an oil-in-water emulsion, with an encapsulation efficiency of 99.6% and a particle loading capacity of 32%. Triggered release of curcumin was achieved by adding deferoxamine, an FDA-approved Fe3+ chelating agent; curcumin release efficiency increased at higher deferoxamine concentrations and lower pH. Triggered release of curcumin induced apoptosis in human triple-negative breast cancer cells; cell viability decreased to 34.3% after 24 h of treatment with the curcumin-loaded nanoparticles and deferoxamine, versus >80% viability without deferoxamine to trigger drug release. The biocompatibility, tunable composition and size, high hydrophobic drug loading, and triggered release capability of this nanoscale coordination polymer make it well-suited for use in anticancer drug delivery.
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影响因子：
5.5
作者：
Jackson, CL;Chanzy, HD;Amis, EJ
通讯作者：
Amis, EJ
影响因子：
4.6
作者：
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作者：
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Nejati-Koshki K
影响因子：
6
作者：
Alberti, Giancarla;Emma, Giovanni;Biesuz, Raffaela
通讯作者：
Biesuz, Raffaela