Wang Jun, Wu YanYan, Liu Kai, Yang Weitao, Zeng Weiwei, Gao Xiaolong, Liu ShiYuan, Zhang Bingbo
Department of Radiology, Tongji Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, The Institute for Biomedical Engineering and Nano Science, School of Medicine, Tongji University, Shanghai 200065, China.
Department of Radiology, The Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
APL Bioeng. 2023 Mar 22;7(1):016115. doi: 10.1063/5.0139929. eCollection 2023 Mar.
The development of a combination of chemo/photothermal therapy could overcome the limitations of single-modality therapy and enhance therapeutic efficacy. In this study, a pH/thermal dual-responsive multifunctional drug delivery system with dual-drug loading and enhanced chemo/photothermal therapy is developed based on polydopamine-coated mesoporous silica-gold nanorods (PDA-AuNRs@MSN). Nanoscale mesoporous silica-gold nanorods encapsulating doxorubicin (DOX) are designed as a core and then modified by polydopamine. The PDA shell not only conjugates with another anticancer bortezomib (Btz) to form pH-sensitive bond through boronic acid and catechol but also acts as a gatekeeper to control the release of doxorubicin and enhance the photothermal effect. Such a nanocarrier not only acts as a contrast agent for PA imaging but also serves as a therapeutic agent for enhanced chemo/photothermal therapy. The DOX and Btz could be released in an on-demand mode under near-infrared light irradiation and acid environment. The tumor size and location could be observed via PA imaging after intravenous injection into 4T1-bearing mice. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibit an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. The integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy and in comparison with single chemotherapy or photothermal therapy. Combined together, D/B-PDA-AuNRs@MSN show pH/thermal-responsive controlled-release and synergistic chemo/photothermal therapy for tumor.
化疗/光热疗法联合应用的发展可以克服单一疗法的局限性并提高治疗效果。在本研究中，基于聚多巴胺包覆的介孔二氧化硅-金纳米棒（PDA-AuNRs@MSN）开发了一种具有双药负载和增强化疗/光热疗法的pH/热双响应多功能药物递送系统。将包裹阿霉素（DOX）的纳米级介孔二氧化硅-金纳米棒设计为核心，然后用聚多巴胺进行修饰。PDA壳层不仅与另一种抗癌药物硼替佐米（Btz）通过硼酸和儿茶酚结合形成pH敏感键，还作为守门人控制阿霉素的释放并增强光热效应。这种纳米载体不仅作为光声成像的造影剂，还作为增强化疗/光热疗法的治疗剂。DOX和Btz可以在近红外光照射和酸性环境下按需释放。静脉注射到荷4T1小鼠体内后，通过光声成像可以观察肿瘤的大小和位置。与AuNRs@MSN相比，PDA-AuNRs@MSN在808nm处表现出增加的近红外（NIR）吸收和增强的光热效应。与单一化疗或光热疗法相比，整合的D/B-PDA-AuNRs@MSN纳米颗粒显示出更高的细胞凋亡率和增强的肿瘤治疗效果。综合起来，D/B-PDA-AuNRs@MSN显示出对肿瘤的pH/热响应控释和协同化疗/光热疗法。
