Stimulus-responsive polymers are promising drug delivery systems for cancer therapy. However, low drug loading and drug leakage of polymeric carriers remain challenges. Here, a crosslinked diselenide-containing micelle was developed with pH/GSH dual responsiveness. Polyesters with multiple diselenide bonds and pendant ketone groups were synthesized by the ring-opening copolymerization of three cyclic monomers (diselenide-containing macrocyclic carbonate, 2-oxepane-1,5-dione, and 1,3-dioxan-2-one). The crosslinked polyester was obtained by the oxime click reaction of pendant ketone groups with hydroxylamine and then self-assembled into crosslinked micelle. This crosslinked micelle remained stable for 14 days, and responded to disassembly under the condition of pH = 5.0 and 10 mM glutathione (GSH). When the crosslinked micelle was loaded with the chemotherapeutic drug DOX, which possessed an active ketone group, the encapsulation efficiency of the crosslinked micelle increased to 91.36 %. The cumulative DOX release reached approximately 45 % under pH = 5.0 and 10 mM GSH. Importantly, the crosslinked diselenide-containing micelle could be taken up in MCF-7 breast cancer cells, responding to the tumor microenvironment and releasing encapsulated DOX. This crosslinked diselenide-containing micelle with pH/GSH dual responsiveness was proven to be a stable and efficient carrier with a promising application.

中文翻译：

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pH/GSH 响应的含二硒化物胶束通过骨架酮肟交联实现有效的药物输送和控释

刺激响应聚合物是用于癌症治疗的有前途的药物输送系统。然而，聚合物载体的低载药量和药物渗漏仍然是挑战。在此，开发了一种具有 pH/GSH 双重响应性的交联二硒化物胶束。通过三种环状单体（含二硒化物大环碳酸酯、2-氧杂环庚烷-1,5-二酮和1,3-二恶烷-2-酮）的开环共聚合成了具有多个二硒化物键和侧酮基团的聚酯。通过侧酮基与羟胺发生肟点击反应得到交联聚酯，然后自组装成交联胶束。该交联胶束在 14 天内保持稳定，并在 pH = 5.0 和 10 mM 谷胱甘肽 (GSH) 的条件下响应分解。当交联胶束负载具有活性酮基的化疗药物DOX时，交联胶束的包封率提高到91.36%。在 pH = 5.0 和 10 mM GSH 下，累积 DOX 释放量达到约 45%。重要的是，含有交联二硒化物的胶束可以被 MCF-7 乳腺癌细胞吸收，对肿瘤微环境做出反应并释放封装的 DOX。这种具有pH/GSH双重响应性的交联二硒化物胶束被证明是一种稳定、高效的载体，具有广阔的应用前景。