Functional block copolymers based on poly(2-oxazoline)s are versatile building blocks for the fabrication of dual-drug delivery nanoparticles (NPs) for anticancer chemotherapy. Core–shell NPs are fabricated from diblock copolymers featuring a long and hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) block coupled to a relatively short and functionalizable poly(2-methylsuccinate-2-oxazoline) (PMestOXA) segment. The PMOXA block stabilizes the NP dispersions, whereas the PMestOXA segment is used to conjugate pterostilbene, a natural bioactive phenolic compound that is used as lipophilic model-drug and constitutes the hydrophobic core of the designed NPs. Subsequent loading of the NPs with clofazimine (CFZ), an inhibitor of the multidrug resistance pumps typically expressed in a large variety of cancer cells, provides an additional function to their formulation. Optimization of the copolymer composition allows the design of polymer scaffolds showing low toxicity and capable of assembling into highly stable NPs dispersions at physiologically relevant pH. In addition, the incorporation of CFZ increases the stability of the NPs and stimulates their internalization by RAW 264.7 cells.

中文翻译：

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聚（2-恶唑啉）–萜二烯嵌段共聚物纳米粒子的双重抗癌药物传递。

基于聚（2-恶唑啉）的功能性嵌段共聚物是用于制造抗癌化学疗法的双重药物输送纳米颗粒（NP）的通用结构单元。核-壳NP由具有长而亲水的聚（2-甲基-2-恶唑啉）（PMOXA）嵌段与相对短且可官能化的聚（2-甲基琥珀酸酯-2-恶唑啉）（PMestOXA）链段的二嵌段共聚物制成。PMOXA嵌段可稳定NP分散体，而PMestOXA片段则用于缀合蝶草萜，一种天然的生物活性酚类化合物，被用作亲脂性模型药物，并构成了所设计NP的疏水核心。NP中随后加入氯氟齐明（CFZ）（一种在多种癌细胞中通常表达的多药耐药泵的抑制剂），为他们的配方提供了额外的功能。共聚物组成的优化允许设计聚合物支架，该支架显示出低毒性并且能够在生理相关的pH值下组装成高度稳定的NPs分散体。此外，CFZ的加入增加了NP的稳定性，并刺激了RAW 264.7细胞对其的内在化。