Pal Kaushik, Singh Swati, Itakura Shoko, Hashimoto Masahiro, Kusamori Kosuke, Nishikawa Makiya
Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India; Department of Mechanical and Industrial Engineering, Indian Institute of Technology Roorkee, Roorkee 247667, India.
Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India; Disease Biology Laboratory, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3(rd) Milestone Faridabad-Gurgaon Expressway, Faridabad 121001, Haryana, India.
Int J Biol Macromol. 2024 Dec;283(Pt 1):137236. doi: 10.1016/j.ijbiomac.2024.137236. Epub 2024 Nov 12.
Amalgamation of near-infrared laser phototherapies with chemotherapy in multi-modal synergistic therapy holds great promise for future precision cancer nanomedicine due to its minimal invasiveness, reduced adverse reactions, and high anticancer efficacy. Herein, CuO nanoparticles were functionalized with photosensitizer molecule, chlorin e6 (Ce6) and coated with polydopamine (PDA) to achieve a drug delivery system (CuO@Ce6-PDA) with photothermal/photodynamic therapy (PTT/PDT). Subsequently, chemical drug PTX was loaded for chemotherapy, and folic acid (FA) serving as cancer-targeting exterior material. Prepared FA@CuO@Ce6-PDA/PTX nanoparticles were nano-sized with favorable biocompatibility, colloidal stability, optimal surface charge, effective PTX loading, and controllable PTX release. In vitro studies on 4T1 cells showed that FA@CuO@Ce6-PDA/PTX had noteworthy synergistic therapeutic antitumour effects featuring chemo/PTT/PDT with IC of 50 μg/mL lower than that FA@CuO@Ce6-PDA/PTX without NIR laser irradiation (225 μg/mL). Additionally, FA@CuO@Ce6-PDA/PTX produced intracellular high reactive oxygen species (ROS) in presence of 660 nm laser, altering mitochondrial membrane potential and promoting tumour cell death. In vivo results indicate nanoplatform could accumulate in tumour spots enabling thermal imaging capabilities and exhibit synergistic therapeutic effect if irradiated with NIR laser (808 and 660 nm), evident from in vitro antitumour assay. Therefore, in vitro finding postulates FA@CuO@Ce6-PDA/PTX could be an intriguing nanoplatform for Chemo/PTT/PDT-based combination therapy.
将近红外激光光疗法与化疗相结合用于多模式协同治疗,因其微创性、不良反应减少和抗癌效果高,对未来精确癌症纳米医学具有巨大潜力。在此,用光敏剂分子二氢卟吩e6(Ce6)对氧化铜纳米颗粒进行功能化,并包覆聚多巴胺(PDA),以实现具有光热/光动力疗法(PTT/PDT)的药物递送系统(CuO@Ce6-PDA)。随后,负载化学药物紫杉醇(PTX)用于化疗,并使用叶酸(FA)作为癌症靶向外部材料。制备的FA@CuO@Ce6-PDA/PTX纳米颗粒呈纳米尺寸,具有良好的生物相容性、胶体稳定性、最佳表面电荷、有效的PTX负载和可控的PTX释放。对4T1细胞的体外研究表明,FA@CuO@Ce6-PDA/PTX具有显著的协同治疗抗肿瘤作用,其化疗/PTT/PDT的半数抑制浓度(IC)为50μg/mL,低于未进行近红外激光照射的FA@CuO@Ce6-PDA/PTX(225μg/mL)。此外,FA@CuO@Ce6-PDA/PTX在660nm激光存在下产生细胞内高活性氧(ROS),改变线粒体膜电位并促进肿瘤细胞死亡。体内结果表明,该纳米平台可在肿瘤部位积聚,具备热成像能力,并且如果用近红外激光(808和660nm)照射,会表现出协同治疗效果,体外抗肿瘤试验证明了这一点。因此,体外研究推测FA@CuO@Ce6-PDA/PTX可能是一种用于基于化疗/PTT/PDT的联合治疗的有趣纳米平台。
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