Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan, Shandong, China; Shenzhen Research Institute of Shandong University, Shenzhen 518057, China.
Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan, Shandong, China.
Colloids Surf B Biointerfaces. 2022 Sep;217:112608. doi: 10.1016/j.colsurfb.2022.112608. Epub 2022 May 31.
Drug resistance and potential cardiotoxicity severely limit the DOX-mediated chemotherapy in clinical. Multi-drug combination is conducive to the realization of multi-modal synergy at the molecular level, which is crucial in drug dose optimization and improvement of therapeutic effect. In this work, fluorescent biotinylated Au Nanoclusters as an active targeting carrier was developed to realize real-time biological imaging and dual-drug delivery simultaneously. DNA toxin doxorubicin (DOX) and tyrosinase inhibitor gefitinib (GEF) were selected as dual-drug models for the treatment of human non-small cell lung cancer. The in vitro and in vivo results showed that dual-drug combination suppressed cancer cell growth more efficiently than any single formula at the same concentrations. GEF can block signaling in target cancer cells with mutated and overactive EGFR, thereby inhibiting tumor growth and metastasis and promoting tumor cell apoptosis. Combined with DOX chemotherapy, it will effectively overcome the problem of DOX resistance. In addition, the dual-drug delivery system produced excellent synergistic therapeutic effects without extra adverse toxicities. It provides a reference for the design and clinical application of the dual-drug delivery system.
耐药性和潜在的心脏毒性严重限制了 DOX 介导的化疗在临床上的应用。多药物联合有利于在分子水平上实现多模式协同作用，这对于药物剂量优化和提高治疗效果至关重要。在这项工作中，荧光生物素化金纳米簇被开发为一种主动靶向载体，以实现实时生物成像和双重药物传递。选择 DNA 毒素阿霉素 (DOX) 和酪氨酸酶抑制剂吉非替尼 (GEF) 作为治疗人非小细胞肺癌的双药模型。体外和体内结果表明，与相同浓度的任何单一配方相比，双药联合更有效地抑制癌细胞生长。GEF 可以阻断具有突变和过度激活 EGFR 的靶癌细胞中的信号转导，从而抑制肿瘤生长和转移并促进肿瘤细胞凋亡。与 DOX 化疗联合使用，将有效克服 DOX 耐药性的问题。此外，双药物递送系统产生了出色的协同治疗效果，而没有额外的不良毒性。它为双药物递送系统的设计和临床应用提供了参考。
