亲水性小分子抗癌药物和超小纳米颗粒(NPs)的肾脏快速清除导致利用率低和一定的副作用,因此,提高肿瘤的靶向性是非常需要的,但也面临着巨大的挑战。提出了一种新颖且通用的β-环糊精(CD)聚集诱导的组装策略,以制造阿霉素(DOX)和CD包被的NP(例如Au)共封装的pH响应型纳米复合材料(NC)。通过在反相微乳液体系中添加DOX×HCl并降低pH值,亲水性CD涂层AuNP快速组装成大型NC。然后多巴胺的原位聚合,并依次与NC表面的Cu2+配位提供了额外的弱酸响应性,化学动力学疗法(CDT),改善了生物相容性和稳定性。随后的肿瘤微环境响应性解离显着改善了其被动肿瘤靶向,生物利用度,成像,和治疗能力,以及促进它们被肿瘤细胞内化和代谢清除,从而减少副作用。聚合的多巴胺和组装的AuNP的组合增强了光热能力,从而通过热放大Cu催化的类Fenton反应进一步促进CDT。体外和体内研究都证实了这些NC作为光声成像引导三峰(热增强CDT,光热疗法,和化疗)协同肿瘤治疗剂,全身毒性最小。
The fast renal clearance of hydrophilic small molecular anticancer drugs and ultrasmall nanoparticles (NPs) results in the low utilization rate and certain side effects, thus improving the tumor targeting is highly desired but faces great challenges. A novel and general β-cyclodextrin (CD) aggregation-induced assembly strategy to fabricate doxorubicin (DOX) and CD-coated NPs (such as Au) co-encapsulated pH-responsive nanocomposites (NCs) is proposed. By adding DOX×HCl and reducing pH in a reversed microemulsion system, hydrophilic CD-coated AuNPs rapidly assemble into large NCs. Then in situ polymerization of dopamine and sequentially coordinating with Cu2+ on the surface of NCs provide extra weak acid responsiveness, chemodynamic therapy (CDT), and improved biocompatibility as well as stability. The subsequent tumor microenvironment responsive dissociation notably improves their passive tumor targeting, bioavailability, imaging, and therapeutic capabilities, as well as facilitates their internalization by tumor cells and metabolic clearance, thereby reducing side effects. The combination of polymerized dopamine and assembled AuNPs reinforces photothermal capability, thus further boosting CDT through thermally amplifying Cu-catalyzed Fenton-like reaction. Both in vitro and in vivo studies confirm the desirable outcomes of these NCs as photoacoustic imaging guided trimodal (thermally enhanced CDT, photothermal therapy, and chemotherapy) synergistic tumor treatment agents with minimal systemic toxicity.