The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Adv Mater. 2022 Mar;34(12):e2110490. doi: 10.1002/adma.202110490. Epub 2022 Feb 14.
The limited anticancer drug library and the frequent occurrence of drug resistance have driven monotherapy-based cancer therapy into a difficult situation. Considering the formidable process of new drug discovery, combination therapy using currently available drugs is a potential alternative. Nevertheless, the barrier between in vitro combination screening and precise in vivo delivery remains insurmountable in the current free-drug- or nanoparticle (NP)-based combination therapy, which substantially hinders the application of combination therapy. Herein, a novel, precise drug delivery strategy to realize efficient and individualized combination therapy is proposed. Nanomedicine (NM) is engineered using a microfluidics-based mixer by combining rationally designed polymeric prodrugs of three commercial chemotherapeutics and a cascade-responsive block copolymer; the NM possesses ratiometric drug loading and synchronized drug release. In addition to quantitative drug loading and precisely controlled drug combination, consistent nanoproperties of these NPs make their in vivo fate predictable. Consequently, tumor growth and metastasis can be effectively inhibited by precisely prescribed NPs derived from in vitro combination screening. This proof-of-concept study clearly reveals the feasibility of overcoming the current drug-library limitations through precise delivery of any predetermined drug combination, facilitating translational research of individualized combination therapy.
有限的抗癌药物库和频繁发生的耐药性使基于单药的癌症治疗陷入困境。考虑到新药发现的艰巨过程，使用现有药物的联合治疗是一种潜在的替代方法。然而，在当前基于游离药物或纳米颗粒 (NP) 的联合治疗中，体外联合筛选和精确的体内输送之间的障碍仍然难以克服，这极大地阻碍了联合治疗的应用。在此，提出了一种新颖的、精确的药物输送策略，以实现高效和个体化的联合治疗。通过结合三种商业化疗药物的合理设计的聚合物前药和级联响应嵌段共聚物，使用基于微流控的混合器来工程化纳米医学 (NM)；NM 具有比例药物负载和同步药物释放。除了定量药物负载和精确控制药物组合外，这些 NPs 的一致纳米特性使它们的体内命运具有可预测性。因此，通过体外联合筛选精确规定的 NPs 可以有效抑制肿瘤生长和转移。这项概念验证研究清楚地表明，通过精确输送任何预定的药物组合来克服当前药物库的局限性是可行的，这有助于个体化联合治疗的转化研究。
