State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, and ‡Center for Mesoscience, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.
ACS Nano. 2016 Jun 28;10(6):5720-9. doi: 10.1021/acsnano.5b07276. Epub 2016 May 27.
The majority of anticancer drugs are poorly water-soluble and thus suffer from rather low bioavailability. Although a variety of delivery carriers have been developed for bioavailability improvement, they are severely limited by low drug loading and undesired side effects. The optimum delivery vehicle would be a biocompatible and biodegradable drug nanoparticle of uniform size with a thin but stable shell, making it soluble, preventing aggregation and enabling targeting. Here, we present a general strategy for the rational design of hydrophobic drug nanoparticles with high drug loading by means of interfacial cohesion and supramolecular assembly of bioadhesive species. We demonstrate that the pathway is capable of effectively suppressing and retarding Ostwald ripening, providing drug nanoparticles with small and uniform size and long-term colloidal stability. The final complex drug nanoparticles provide higher tumor accumulation, negligible toxicity, and enhanced antitumor activity, superior to commercial formulations. Our findings demonstrate that local, on-demand coating of hydrophobic nanoparticles is achievable through cooperation and compromise of interfacial adhesion and assembly.
大多数抗癌药物的水溶性较差，因此生物利用度较低。尽管已经开发了多种输送载体来提高生物利用度，但它们受到载药量低和不良副作用的严重限制。理想的输送载体应该是具有均匀大小的生物相容性和可生物降解的药物纳米颗粒，其具有薄但稳定的外壳，使其具有可溶性、防止聚集和靶向性。在这里，我们提出了一种通过界面内聚和生物粘附物质的超分子组装来合理设计具有高载药量的疏水性药物纳米颗粒的通用策略。我们证明，该途径能够有效地抑制和延缓奥斯特瓦尔德成熟，为药物纳米颗粒提供小而均匀的尺寸和长期胶体稳定性。最终的复合药物纳米颗粒提供了更高的肿瘤积累、可忽略的毒性和增强的抗肿瘤活性，优于商业制剂。我们的研究结果表明，通过界面粘附和组装的合作和妥协，可以实现对疏水性纳米颗粒的局部按需涂层。
