Zhang Jiaojiao, Huang Han, Xue Lei, Zhong Liping, Ge Wei, Song Xuejiao, Zhao Yongxiang, Wang Wenjun, Dong Xiaochen
Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, China.
National Center for International Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Theranostics, Guangxi Medical University, Guangxi, 530021, China.
Biomaterials. 2020 Oct;256:120211. doi: 10.1016/j.biomaterials.2020.120211. Epub 2020 Jul 1.
Intelligent drug delivery systems (DDS), integrating with multi-modal imaging guidance and controlled drug release, have practical significance in enhancing the therapeutic efficiency of tumors. Herein, fluorinated aza-boron-dipyrromethene (NBF) with high near-infrared absorption is synthesized by introducing nonadecafluorodecanoic acid into aza-BODIPY via the amide bond. Through the co-precipitation methods, nanoparticles (NPs) based on NBF are fabricated and the obtained NBF NPs can not only load with DOX with a high loading efficiency (25%, DNBF NPs), but also absorb PFC droplets (1H-perfluoropentane) with bp of 42 °C because of the fluorinated chains inside NBF NPs (PDNBF NPs). Under 808-nm laser irradiation, the hyperthermia effect of NBF could induce the liquid-gas phase transition of PFC droplets, triggering the burst release of DOX and enhancing echo signals for ultrasound imaging as well. With efficient enrichment of PDNBF NPs at tumor site as revealed by in vivo ultrasound imaging and photoacoustic imaging, significant improvement in inhibiting tumor growth is achieved with PDNBF NPs under laser irradiation without noticeable side effects. The work presents a multifunctional organic DDS with great biocompatibility, high drug loading efficiency and light-stimuli-responsive drug release, which provides a new strategy for the manufacture of intelligent composite theranostic nanoplatform.
智能给药系统（DDS）与多模态成像引导和可控药物释放相结合，在提高肿瘤治疗效率方面具有实际意义。在此，通过酰胺键将十九氟癸酸引入氮杂硼二吡咯（aza-BODIPY）中，合成了具有高近红外吸收的氟化氮杂硼二吡咯（NBF）。通过共沉淀法制备了基于NBF的纳米颗粒（NPs），所得的NBF NPs不仅能以高负载效率（25%，DNBF NPs）负载阿霉素（DOX），还由于NBF NPs内部的氟化链而能吸收沸点为42℃的全氟戊烷液滴（1H-全氟戊烷）（PDNBF NPs）。在808 nm激光照射下，NBF的热疗效应可诱导PFC液滴的液-气相转变，触发DOX的突发释放，并增强超声成像的回波信号。体内超声成像和光声成像显示，PDNBF NPs在肿瘤部位有效富集，在激光照射下，PDNBF NPs对肿瘤生长的抑制作用显著改善，且无明显副作用。这项工作提出了一种具有良好生物相容性、高药物负载效率和光刺激响应药物释放的多功能有机DDS，为智能复合诊疗纳米平台的制造提供了一种新策略。
