Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Int J Mol Sci. 2022 Oct 17;23(20):12420. doi: 10.3390/ijms232012420.
Polydopamine (PDA), a biomaterial inspired by marine mussels, has attracted interest in cancer nanomedicine due to its photothermal properties, nanoparticle coating, and pi-pi stacking-based drug encapsulation abilities. Despite numerous one-pot and post-polymerization modifications, PDA copolymers have not been sufficiently studied in the context of stabilizing hydrophobic drugs in the process of nanoprecipitation. In this study, we tested combinatorial panels of comonomers with PDA to optimize drug loading efficiency, particle size and stability of nano formulations made via drug nanoprecipitation. As a selection criterion for optimal comonomers, we used drug aggregation-induced emission (AIE). We identified 1,1,2-Trimethyl-3-(4-sulfobutyl)benz[e]indolium (In820) as a novel and highly useful comonomer for catecholamines and optimized the conditions for its incorporation into PDA copolymers used for drug nanoprecipitation. Surprisingly, it was superior to polyethylene glycol modifications in every aspect. The leading copolymer, poly(dopamine)-poly(L-dopa)-co-In820 (PDA-PDO-In820 1:1:1), was shown to be a good stabilizer for several hydrophobic drugs. The resulting nanoparticles showed stability for up to 15 days, high encapsulation efficiency of at least 80%, low toxicity, and high antitumor efficacy in vitro. Nanoprecipitation of hydrophobic drugs can be greatly enhanced by the use of PDA copolymers containing In820, which are easy-to-prepare and highly effective stabilizers.
聚多巴胺（PDA）是一种受海洋贻贝启发的生物材料，由于其光热性质、纳米粒子涂层和基于 π-π 堆积的药物包封能力，在癌症纳米医学中引起了关注。尽管进行了许多一锅法和聚合后修饰，但在纳米沉淀过程中稳定疏水性药物方面，PDA 共聚物尚未得到充分研究。在这项研究中，我们测试了 PDA 与共聚单体的组合面板，以优化通过药物纳米沉淀制备的纳米制剂的药物载药效率、粒径和稳定性。作为最佳共聚单体的选择标准，我们使用了药物聚集诱导发射（AIE）。我们确定 1,1,2-三甲基-3-(4-磺丁基)苯并[e]吲哚鎓（In820）作为儿茶酚胺的新型且非常有用的共聚单体，并优化了其掺入用于药物纳米沉淀的 PDA 共聚物的条件。令人惊讶的是，它在各个方面都优于聚乙二醇修饰。主导共聚物，聚（多巴胺）-聚（L-多巴）-co-In820（PDA-PDO-In820 1:1:1），被证明是几种疏水性药物的良好稳定剂。所得纳米颗粒在长达 15 天的时间内保持稳定，至少 80%的高包封效率、低毒性和体外高抗肿瘤功效。通过使用含有 In820 的 PDA 共聚物，可以大大增强疏水性药物的纳米沉淀，这些共聚物易于制备且具有高效的稳定性。
