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ROP and ATRP fabricated redox sensitive micelles based on PCL-SS-PMAA diblock copolymers to co-deliver PTX and CDDP for lung cancer therapy
Colloids and Surfaces B: Biointerfaces ( IF 5.4 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.colsurfb.2020.111443
Yu-Lun Lo, Xiao-Shan Huang, Hsuan-Ying Chen, Yuan-Chun Huang, Zi-Xian Liao, Li-Fang Wang

Combining dual drugs in one vehicle to cancer cells offers spatiotemporal localization of drug at the site of action, leading to synergistic therapeutic effects and reduced side effects. To improve pH/redox responsiveness to the tumor microenvironments for cancer therapy, a pH/redox-responsive micelle based on poly(ε-caprolactone)-SS-poly(methacrylic acid) (PCL-SS-PMAA) diblock copolymer was fabricated for dual drug delivery. The PCL-SS-PMAA was formulated into a core-shell micelle (PSPm) in an aqueous solution. The critical micelle concentration (CMC) values of PSPm were 7.94 × 10−3 mg mL-1 at pH 5.0 and 1.00 × 10-2 mg mL-1 at pH 7.4. The hydrodynamic diameters of PSPm were within 210–270 nm, depending on pH values. Changes in morphology and size of PSPm were clearly observed before and after exposure to a reducing agent. Paclitaxel (PTX) was encapsulated into the core and cisplatin (CDDP) was chelated on the shell of PSPm, with both PTX and CDDP being efficiently released from PSPm in the presence of a reducing agent in an acid condition. MTT and annexin V/propidium iodide dual staining results demonstrated that co-loading of CDDP and PTX into PSPm had a synergistic effect in killing lung cancer cells and exerted superior antitumor activity over the combination of single drug-loaded PSPm or the combination of free-CDDP and free-PTX at equivalent drug amounts. Hence, encapsulating the dual drugs into PSPm exhibits a synergistic effect for potential lung cancer therapy.



中文翻译:

ROP和ATRP基于PCL-SS-PMAA二嵌段共聚物制备了氧化还原敏感胶束,以共同递送PTX和CDDP用于肺癌治疗

将一种药物中的两种药物与癌细胞结合使用可将药物在作用部位时空定位,从而产生协同治疗效果并减少副作用。为了提高pH /氧化还原对肿瘤微环境的癌症治疗的响应性,制备了基于聚(ε-己内酯)-SS-聚(甲基丙烯酸)(PCL-SS-PMAA)二嵌段共聚物的pH /氧化还原响应胶束药物输送。将PCL-SS-PMAA在水溶液中配制成核壳胶束(PSPm)。PSPM的临界胶束浓度(CMC)值分别为7.94×10 -3毫克毫升-1在pH 5.0和1.00×10 -2毫克毫升-1在pH 7.4下。PSPm的流体力学直径在210-270 nm之间,具体取决于pH值。暴露于还原剂之前和之后,PSPm的形态和大小均发生了明显变化。将紫杉醇(PTX)封装到核中,将顺铂(CDDP)螯合在PSPm的外壳上,在酸性条件下,在还原剂的存在下,PTX和CDDP均可从PSPm有效释放。MTT和Annexin V /碘化丙啶双重染色结果表明,将CDDP和PTX共同装载到PSPm中具有杀死肺癌细胞的协同作用,并且比单一药物装载的PSPm或游离的PSPm的结合具有更好的抗肿瘤活性。 CDDP和游离PTX的用量相等。因此,

更新日期:2020-11-02
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