Much knowledge on the small-molecule self-assemblies (Mw<5000) via covalent capture are utilized to develop a reversible crosslinked micelles-based nanosystems for drug delivery, which exhibit the significant advantages than the traditional polymeric micelles-based nanosystems with regards of stability, monomer purity and facile fabrication. In this study, a novel reversible small-molecule phosphatidylcholine was synthesized which can be polymerized and de-polymerized via thiol-disulfide redox cycle. Benefiting from its monomer purity and potential biodegradability, lipoic acid-bearing phosphorylcholine (di-LA-PC) conjugate undergoes assembly to form crosslinked micelles applicable for redox-dependent drug delivery. Di-LA-PC micelles, as an effective nanocarrier of paclitaxel (PTX), maintained excellent stability in physiological condition but rapidly de-polymerized in reductive environment. The micelles exhibited efficient cellular internalization capability, as well as effectively induced the deaths of cancer cell lines as revealed in MTT, apoptosis and cell cycle tests. Pharmacokinetics studies demonstrated the prolonged circulation of incorporated PTX in bloodstream, which could increase its accumulation into tumor via enhanced permeability and retention (EPR) effect. More importantly, PTX-loaded micelles displayed prominent in vivo therapeutic performance and low toxicity in 4T1 xenograft tumors model. This strategy of using small-molecule polymerizable phosphatidylcholine offers an innovative approach for triggered drugs delivery to combat cancer.

利用通过共价捕获获得的小分子自组装体（Mw <5000）的丰富知识来开发可逆交联的基于胶束的纳米系统用于药物输送，在稳定性方面，与传统的基于聚合物胶束的纳米系统相比，它们具有明显的优势。 ，单体纯度高，制造容易。在这项研究中，一种新型的可逆的小分子的磷脂酰胆碱合成可聚合和脱聚合经由硫醇二硫化物的氧化还原循环。得益于其单体纯度和潜在的生物可降解性，带有硫辛酸的磷酸胆碱（di-LA-PC）偶联物经过组装后形成交联的胶束，可用于依赖氧化还原的药物递送。Di-LA-PC胶束作为紫杉醇（PTX）的有效纳米载体，在生理条件下保持出色的稳定性，但在还原性环境中迅速解聚。胶束表现出有效的细胞内在化能力，并有效诱导癌细胞系的死亡，如MTT，凋亡和细胞周期测试所示。药代动力学研究表明掺入的PTX在血液中的循环时间延长，这可能通过以下途径增加其在肿瘤中的蓄积增强的渗透性和保留（EPR）效果。更重要的是，载有PTX的胶束在4T1异种移植肿瘤模型中显示出突出的体内治疗性能和低毒性。这种使用小分子可聚合磷脂酰胆碱的策略为触发药物的递送提供了一种创新的方法来对抗癌症。