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Near-Infrared Fluorescent Dye-Decorated Nanocages to Form Grenade-like Nanoparticles with Dual Control Release for Photothermal Theranostics and Chemotherapy
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-03-05 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00088
Chun-Yen Lin,Ming-Jium Shieh

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.

中文翻译:

近红外荧光染料修饰的纳米笼形成具有双重控制释放作用的手榴弹样纳米颗粒,用于光热治疗和化学疗法

近来,已经广泛研究了用于递送抗癌药物的纳米颗粒(NP)。在这里,开发了一种双重控制药物释放方式,该方式使用负载阿霉素(DOX)和ADS-780近红外(NIR)荧光染料修饰的NP(ADNIR NP)的天然蛋白质载铁蛋白。ADNIR NP充当手榴弹,在激光照射(光热疗法,PTT)后引爆目标肿瘤部位,并爆炸成簇状战斗部(载有铁蛋白的DOX纳米笼,AF-DOX NC),进一步破坏肿瘤细胞(化学疗法)。研究表明,在低pH细胞间环境中,光会破坏NP的手榴弹状结构,从而释放AF-DOX NC以及NC中的DOX。体外体内研究表明,AF-DOX NCs的结构被分解以释放DOX,然后DOX在酸性环境中杀死细胞器中的癌细胞。体内研究表明,使用IIR成像系统,用NIR染料修饰的ADNIR NP有助于追踪肿瘤部位累积的NP。总体而言,具有双释放机制的靶向ADNIR NP已开发用于光热治疗和化学疗法。这种方式在癌症治疗以及药物传递和成像的临床翻译中具有很高的应用潜力。
更新日期:2018-03-05
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