Department of Chemistry , Pohang University of Science and Technology (POSTECH) , Pohang 37673 , Republic of Korea.
Center for Self-assembly and Complexity , Institute for Basic Science (IBS) , Pohang , 37673 , Republic of Korea.
Biomacromolecules. 2018 Jun 11;19(6):2202-2213. doi: 10.1021/acs.biomac.8b00290. Epub 2018 Apr 30.
Incorporation of a desired stimuli-responsive unit in a stereospecific manner at the specific location within a nonlinear block copolymer architecture is a challenging task in synthetic polymer chemistry. Herein, we report a facile and versatile method to synthesize AB miktoarm block copolymers bearing a singlet oxygen (O)-labile regio and stereospecific β-aminoacrylate linkage with 100% E-configuration at the junction via a combination of amino-yne click chemistry and ring opening polymerization. Using this strategy, a series of O-responsive AB amphiphilic miktoarm (MA) copolymers composed of hydrophilic polyethylene glycol (PEG) as the A constituent and hydrophobic polycaprolactone (PCL) as the B constituent (MA-PEG- b-PCL) was synthesized by varying the block length of PCL. The self-assembly characteristics of these well-defined MA-PEG- b-PCL copolymers in an aqueous condition were studied by solvent displacement and thin-film hydration method, and their morphologies were investigated using transmission electron microscopy. The copolymers formed spherical, cylindrical, or lamella morphologies, depending on the chain length and preparation conditions. A hydrophobic photosensitizer chlorin e6 (Ce6) and anticancer drug doxorubicin (DOX) were efficiently encapsulated into the hydrophobic core of MA-PEG- b-PCL copolymer micelles. These coloaded micelles were taken up by human breast cancer (MDA-MB-231) cells. Upon red laser light irradiation, the O-generated by the Ce6 induced photocleavage of the β-aminoacrylate moiety, leading to the dissociation of the micellar structure and triggered intracellular drug release for effective therapy. Overall, rapid disassembly upon O generation and subsequent controlled intracellular drug release suggested that these micelles bearing β-aminoacrylate linkage have a huge potential for on-demand drug delivery.
在非线性嵌段共聚物结构中，将所需的刺激响应单元以立体专一的方式结合到特定位置是合成聚合物化学中的一项具有挑战性的任务。在此，我们报告了一种简便而通用的方法，通过氨基-炔点击化学和开环聚合的组合，在 AB 型杂臂嵌段共聚物中合成了具有单一氧（O）不稳定区域和立体专一性β-氨基丙烯酸酯键的 AB 型杂臂嵌段共聚物，其在键合处具有 100% E-构型。使用该策略，通过改变 PCL 的嵌段长度，合成了一系列由亲水性聚乙二醇（PEG）作为 A 组分和疏水性聚己内酯（PCL）作为 B 组分组成的 O 响应性 AB 两亲性杂臂（MA）共聚物（MA-PEG- b-PCL）。通过溶剂置换和薄膜水合方法研究了这些具有良好定义的 MA-PEG- b-PCL 共聚物在水介质中的自组装特性，并通过透射电子显微镜研究了它们的形态。共聚物根据链长和制备条件形成球形、圆柱形或层状形态。疏水性光敏剂氯[e6]（Ce6）和抗癌药物阿霉素（DOX）被有效地包封在 MA-PEG- b-PCL 共聚物胶束的疏水性内核中。这些共载胶束被人乳腺癌（MDA-MB-231）细胞摄取。在红光激光照射下，Ce6 产生的 O 引发β-氨基丙烯酸酯部分的光裂解，导致胶束结构的解离，并触发细胞内药物释放以进行有效治疗。总的来说，O 生成时的快速解组装和随后的受控细胞内药物释放表明，这些具有β-氨基丙烯酸酯键的胶束具有按需药物递送的巨大潜力。
