Department of Chemical & Biological Engineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, Republic of Korea.
ChemMedChem. 2018 Jul 18;13(14):1459-1468. doi: 10.1002/cmdc.201800202. Epub 2018 Jun 14.
Herein we describe fluorescence resonance energy transfer (FRET) for a pH/redox-activatable fluorescent carbon dot (FNP) to realize "off-on" switched imaging-guided controllable photothermal therapy (PTT). The FNP is a carbonized self-crosslinked polymer that allows IR825 loading (FNP[IR825]) via hydrophobic interactions for cancer therapy. Fluorescence bioimaging was achieved by the internalization of FNP(IR825) into tumor cells, wherein glutathione (GSH) disulfide bonds are reduced, and benzoic imine groups are cleaved under acidic conditions. The release of IR825 from the FNP core in this system may be used to efficiently control PTT-mediated cancer therapy via its photothermal conversion after near-infrared (NIR) irradiation. In vitro and in vivo cellular uptake studies revealed efficient uptake of FNP(IR825) by tumor cells to treat the disease site. In this way we demonstrated in mice that our smart nanocarrier can effectively kill tumor cells under exposure to a NIR laser, and that the particles are biocompatible with various organs. This platform responds sensitively to the exogenous environment inside the cancer cells and may selectively induce the release of PTT-mediated cytotoxicity. Furthermore, this platform may be useful for monitoring the elimination of cancer cells through the fluorescence on/off switch, which can be used for various applications in the field of cancer cell therapy and diagnosis.
在此,我们描述了荧光共振能量转移(FRET)用于 pH/氧化还原激活的荧光碳点(FNP),以实现“关-开”切换成像引导可控光热治疗(PTT)。FNP 是一种碳化自交联聚合物,允许通过疏水相互作用加载 IR825(FNP[IR825])用于癌症治疗。荧光生物成像通过 FNP(IR825)被内化到肿瘤细胞中来实现,其中谷胱甘肽(GSH)二硫键在酸性条件下被还原,苯并亚胺基团被裂解。在该系统中,IR825 从 FNP 核中的释放可用于通过近红外(NIR)照射后的光热转换来有效控制 PTT 介导的癌症治疗。体外和体内细胞摄取研究表明,肿瘤细胞能够有效摄取 FNP(IR825)来治疗疾病部位。通过这种方式,我们在小鼠中证明了我们的智能纳米载体可以在暴露于近红外激光下有效杀死肿瘤细胞,并且这些颗粒与各种器官具有生物相容性。该平台对癌细胞内的外源性环境敏感,并可选择性地诱导 PTT 介导的细胞毒性的释放。此外,该平台可用于通过荧光开关来监测癌细胞的消除,这可用于癌症细胞治疗和诊断领域的各种应用。