Multifunctional nanocarriers of two or more anticancer drugs with different pharmacological mechanisms are being developed for combination therapy, which aims at achieving synergistic effects in cancer treatment and overcoming the increasingly common problem of drug resistance. This contribution reports the fabrication of functional nanosized micellar carriers of doxorubicin (DOX) and caffeic acid phenethyl ester (CAPE) via coassembly of two well-defined amphiphilic ABA triblock copolymers comprising identical hydrophobic poly(ε-caprolactone) (PCL) blocks and different hydrophilic segments – poly(ethylene oxide) (PEO) or poly(acrylic acid) (PAA). CAPE was embedded into the PCL core via hydrophobic interactions, while DOX was loaded within a mixed PAA/PEO corona layer through complexation. The main physico-chemical properties of blank and dual drug-loaded micelles were investigated using dynamic and electrophoretic light scattering and transmission electron microscopy. Loading of CAPE and DOX increased the size and size distribution of carriers to some extent. However, the mixed micellar system was characterized by good colloidal stability and sustained release of the two drugs. The cytotoxic effect of DOX/CAPE-loaded mixed micelles in drug-resistant lymphoma cells expressing the multidrug resistance (MDR1) gene (L5178Y MDR1) was assessed. Functional micellar nanocarriers for codelivery of doxorubicin (DOX) and caffeic acid phenethyl ester (CAPE) were successfully developed via coassembly of PEO113-b-PCL35-b-PEO113 and PAA13-b-PCL35-b-PAA13. CAPE was entrapped into the PCL core via hydrophobic interactions, while DOX was loaded in the middle layer through complexation between the amino and carboxylic groups of DOX and PAA. The dual drug-loaded micelles exhibited superior colloidal stability and sustained drug release profiles. The dual drug -loaded system suppressed the proliferation of mouse T-lymphoma L5178Y MDR1 cells more effectively than the single drug-loaded micelles, suggesting a synergistic effect.

中文翻译：

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用于阿霉素和咖啡酸苯乙酯共递送的混合胶束系统：设计和增强的抗肿瘤活性

正在开发具有不同药理机制的两种或多种抗癌药物的多功能纳米载体用于联合治疗，旨在在癌症治疗中实现协同效应，克服日益普遍的耐药性问题。该贡献报告了通过包含相同疏水性聚（ε-己内酯）（PCL）嵌段和不同亲水性的两种明确定义的两亲性 ABA 三嵌段共聚物的共组装，制备了多柔比星（DOX）和咖啡酸苯乙酯（CAPE）的功能性纳米胶束载体。段 – 聚（环氧乙烷）（PEO）或聚（丙烯酸）（PAA）。CAPE 通过疏水相互作用嵌入到 PCL 核心中，而 DOX 通过复合负载在混合的 PAA/PEO 电晕层中。使用动态和电泳光散射和透射电子显微镜研究了空白和双载药胶束的主要理化性质。CAPE和DOX的加载在一定程度上增加了载体的尺寸和尺寸分布。然而，混合胶束体系的特点是良好的胶体稳定性和两种药物的缓释。评估了载有 DOX/CAPE 的混合胶束在表达多药耐药 (MDR1) 基因 (L5178Y MDR1) 的耐药淋巴瘤细胞中的细胞毒性作用。通过PEO113-b-PCL35-b-PEO113和PAA13-b-PCL35-b-PAA13的共组装，成功开发了用于阿霉素（DOX）和咖啡酸苯乙酯（CAPE）共递送的功能性胶束纳米载体。CAPE 通过疏水相互作用被包埋到 PCL 核心中，而DOX通过DOX和PAA的氨基和羧基之间的络合负载在中间层。双载药胶束表现出优异的胶体稳定性和持续的药物释放曲线。双重载药系统比单一载药胶束更有效地抑制小鼠 T 淋巴瘤 L5178Y MDR1 细胞的增殖，表明具有协同作用。