CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and Engineering , University of Science and Technology of China , Hefei , Anhui 230026 , China.
Biomacromolecules. 2018 Jun 11;19(6):2071-2081. doi: 10.1021/acs.biomac.8b00253. Epub 2018 Apr 12.
We report on the preparation of photo- and reduction-responsive diblock copolymers through reversible addition-fragmentation chain transfer (RAFT) polymerization of a coumarin-based disulfide-containing monomer (i.e., CSSMA) using a poly(ethylene oxide) (PEO)-based macroRAFT agent. The resulting amphiphilic PEO- b-PCSSMA copolymers self-assembled into polymersomes with hydrophilic PEO shielding coronas and hydrophobic bilayer membranes. Upon irradiating the polymersomes with visible light (e.g., 430 nm), the coumarin moieties within the bilayer membranes were cleaved with the generation of primary amine groups, which spontaneously underwent inter/intrachain amidation reactions with the ester moieties, thereby tracelessly cross-linking and permeating the bilayer membranes. Notably, this process only gave rise to the release of small molecule payloads (e.g., doxorubicin hydrochloride, DOX) while large molecule encapsulants (e.g., Texas red-labeled dextran, TR-dextran) were retained within the cross-linked polymersomes due to the preservation of the integrity of the vesicular nanostructures. However, cross-linked polymersomes undergo further structural disintegration upon incubation with glutathione (GSH) due to the scission of disulfide linkages, resulting in the release of macromolecular payloads. Thus, dual-stimuli responsive polymersomes with tracelessly cross-linkable characteristics enable sequential release of payloads with spatiotemporal precision, which could be of promising applications in synergistic loading and programmed release of therapeutics.
我们通过可逆加成-断裂链转移（RAFT）聚合，使用基于聚乙二醇（PEO）的大分子 RAFT 试剂，制备了光响应和还原响应的二嵌段共聚物。该共聚物以香豆素基含二硫键的单体（即 CSSMA）为单体。所得两亲性 PEO-b-PCSSMA 共聚物自组装成聚合物囊泡，具有亲水性 PEO 屏蔽冠和疏水性双层膜。当聚合物囊泡用可见光（例如 430nm）照射时，双层膜内的香豆素部分被切断，生成伯胺基团，这些基团自发地与酯部分进行链内/链间酰胺化反应，从而无痕交联和渗透双层膜。值得注意的是，这个过程仅导致小分子药物（如盐酸阿霉素，DOX）的释放，而大分子封装物（如 Texas 红标记的葡聚糖，TR-葡聚糖）则由于囊泡纳米结构完整性的保留而保留在交联聚合物囊泡内。然而，交联聚合物囊泡在与谷胱甘肽（GSH）孵育时会进一步发生结构解体，这是由于二硫键的断裂，导致大分子药物的释放。因此，具有无痕交联特性的双重刺激响应聚合物囊泡能够实现具有时空精度的药物顺序释放，这在协同加载和编程释放治疗药物方面具有广阔的应用前景。
