Institute of Biomedical Engineering, College of Medicine and College of Engineering , National Taiwan University , No. 1, Section 1, Jen-Ai Road , Taipei 100 , Taiwan.
Department of Oncology , National Taiwan University Hospital and College of Medicine , #7, Chung-Shan South Road , Taipei 100 , Taiwan.
Bioconjug Chem. 2018 Apr 18;29(4):1384-1398. doi: 10.1021/acs.bioconjchem.8b00088. Epub 2018 Mar 12.
Recently, nanoparticles (NPs) have been widely investigated for delivery of anticancer drugs. Here, a dual control drug-release modality was developed that uses naturally occurring protein apoferritin loaded with doxorubicin (DOX) and ADS-780 near-infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs). ADNIR NPs act as a grenade to detonate the targeted tumor site following laser irradiation (photothermal therapy, PTT) and explode into cluster warheads (apoferritin-loaded DOX nanocages, AF-DOX NCs) that further destroy the tumor cells (chemotherapy). Light was shown to disrupt the grenade-like structure of NPs to release AF-DOX NCs as well as DOX from NCs in low-pH intercellular environments. In vitro and in vivo studies showed that the structure of AF-DOX NCs was disassembled to release DOX, which then killed the cancer cells in organelles with acidic environments. In vivo studies showed that the ADNIR NP-decorated with NIR dye facilitated tracking of the accumulated NPs at the tumor site using an IVIS imaging system. Overall, targeted ADNIR NPs with dual-release mechanisms were developed for use in photothermal theranostic and chemotherapy. This modality has high potential for application in cancer treatment and clinical translation for drug delivery and imaging.
最近，纳米颗粒 (NPs) 已被广泛研究用于输送抗癌药物。在这里，开发了一种双重控制药物释放模式，该模式使用天然存在的载有阿霉素 (DOX) 和 ADS-780 近红外 (NIR) 荧光染料的脱铁蛋白 (apoferritin) 负载 NPs (ADNIR NPs)。ADNIR NPs 可作为手榴弹，在激光照射（光热疗法，PTT）后引爆靶向肿瘤部位，并爆炸成集束弹头（载有 DOX 的脱铁蛋白纳米笼，AF-DOX NCs），进一步破坏肿瘤细胞（化疗）。结果表明，光可以破坏 NPs 的手榴弹状结构，以在低 pH 细胞内环境中从 NCs 中释放 AF-DOX NCs 和 DOX。体外和体内研究表明，AF-DOX NCs 的结构被拆开以释放 DOX，然后 DOX 在具有酸性环境的细胞器中杀死癌细胞。体内研究表明，用 NIR 染料修饰的 ADNIR NP 有助于使用 IVIS 成像系统在肿瘤部位跟踪累积的 NPs。总的来说，开发了具有双重释放机制的靶向 ADNIR NPs，用于光热治疗和化学治疗。这种模式在癌症治疗和临床转化为药物输送和成像方面具有很高的应用潜力。
