Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran.
Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran; Environmental Applied Science and Management, Ryerson University, Toronto, Canada.
Acta Biomater. 2018 Aug;76:239-256. doi: 10.1016/j.actbio.2018.05.031. Epub 2018 Jun 19.
The oxidation-reduction (redox)-responsive micelle system is based on a diselenide-containing triblock copolymer, poly(ε-caprolactone)-bis(diselenide-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate) [PCL-(SeSe-mPEG/PEG-FA)]. This has helped in the development of tumor-targeted delivery for hydrophobic anticancer drugs. The diselenide bond, as a redox-sensitive linkage, was designed in such a manner that it is located at the hydrophilic-hydrophobic hinge to allow complete collapse of the micelle and thus efficient drug release in redox environments. The amphiphilic block copolymers self-assembled into micelles at concentrations higher than the critical micelle concentration (CMC) in an aqueous environment. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses showed that the micelles were spherical with an average diameter of 120 nm. The insoluble anticancer drug paclitaxel (PTX) was loaded into micelles, and its triggered release behavior under different redox conditions was verified. Folate-targeting micelles showed an enhanced uptake in 4T1 breast cancer cells and in vitro cytotoxicity by flow cytometry and (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, respectively. Delayed tumor growth was confirmed in the subcutaneously implanted 4T1 breast cancer in mice after intraperitoneal injection. The proposed redox-responsive copolymer offers a new type of biomaterial for drug delivery into cancer cells in vivo.
On-demand drug actuation is highly desired. Redox-responsive polymeric DDSs have been shown to be able to respond and release their cargo in a selective manner when encountering a significant change in the potential difference, such as that present between cancerous and healthy tissues. This study offers an added advantage to the field of redox-responsive polymers by reporting a new type of shell-sheddable micelle based on an amphiphilic triblock co-polymer, containing diselenide as a redox-sensitive linkage. The linkage was smartly located at the hydrophilic-hydrophilic bridge in the co-polymer offering complete collapse of the micelle when exposed to the right trigger. The system was able to delay tumor growth and reduce toxicity in a breast cancer tumor model following intraperitoneal injection in mice.
氧化还原（redox）响应胶束系统基于一种含有二硒键的嵌段共聚物，聚（ε-己内酯）-双（二硒键-甲氧基聚（乙二醇）/聚（乙二醇）-叶酸）[PCL-（SeSe-mPEG/PEG-FA）]。这有助于开发用于疏水性抗癌药物的肿瘤靶向递送。二硒键作为一种氧化还原敏感的键，被设计成位于亲水-亲油铰链处，以使胶束完全坍塌，从而在氧化还原环境中有效释放药物。两亲嵌段共聚物在高于临界胶束浓度（CMC）的浓度下在水相中自组装成胶束。动态光散射（DLS）和透射电子显微镜（TEM）分析表明，胶束为球形，平均直径为 120nm。不溶性抗癌药物紫杉醇（PTX）被载入胶束中，并验证了其在不同氧化还原条件下的触发释放行为。叶酸靶向胶束在 4T1 乳腺癌细胞中的摄取量增加，并通过流式细胞术和（3-（4,5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑）（MTS）测定法证实了体外细胞毒性增强。在皮下植入 4T1 乳腺癌的小鼠中，经腹腔注射后，确认肿瘤生长延迟。所提出的氧化还原响应共聚物为体内将药物递送到癌细胞提供了一种新型生物材料。
按需药物触发是人们所高度期望的。氧化还原响应聚合物给药系统已被证明能够在遇到明显的电位差变化（例如在癌组织和健康组织之间）时以选择性的方式响应并释放其货物。本研究通过报道一种基于两亲性嵌段共聚物的新型壳可脱落胶束，为氧化还原响应聚合物领域提供了一个额外的优势，该共聚物含有二硒键作为氧化还原敏感键。该键被巧妙地定位在共聚物的亲水-亲水桥中，当暴露于正确的触发时，共聚物完全坍塌。该系统能够在小鼠腹腔注射后，在乳腺癌肿瘤模型中延迟肿瘤生长并降低毒性。
