期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 8, 期 2, 页码 880-892出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.1c01418
关键词
dual-mode Imaging; RGD; MMP2; photodynamic therapy; lung cancer
In this study, a therapeutic and diagnostic nanosystem was synthesized using a self-assembling strategy for tumor-targeted dual-mode near-infrared fluorescence/magnetic resonance imaging and photodynamic therapy. The nanosystem showed low cytotoxicity and high endocytosis efficiency, and exhibited promising potential for cancer clinical diagnosis and therapy.
In this study, the self-assembling strategy was used to synthesize a therapeutic and diagnostic nanosystem for tumortriggered targeting dual-mode near-infrared fluorescence (NIRF)/ magnetic resonance (MR) imaging and photodynamic therapy applications. This theranostic nanosystem was synthesized based on the self-assembling of the short peptide (PLGVRGRGDC) and the gadolinium chelator (diethylenetriamine pentaacetic acid) functionalized amphiphilic DSPE-PEG2000, followed by loading with the insoluble photosensitizer therapeutic agent chlorin e6 (Ce6). The formed theranostic nanosystem can accumulate in the matrix metalloproteinase 2 (MMP2) rich tumor sites guided by the enhanced permeability and retention effect and MMP2-substrate peptide (PLGVR) targeting. After PLGVR was hydrolyzed in the tumor microenvironment by MMP2, the nanosystem was actively taken up by tumor cells via Arg-Gly-Asp (RGD) peptide-mediated internalization. With the coexistence of gadolinium and Ce6, the formed nanosystem can be used for both NIRF/MR dual-mode imaging and photodynamic therapy. These tumor-triggered targeting self-assembled nanoparticles with low cytotoxicity and high endocytosis efficiency can efficiently induce A549 cancer cell apoptosis under laser irradiation. Meanwhile, they possessed enhanced tumor-targeted NIRF/MR imaging ability and efficiently inhibited tumor growth with minimal side effects in mice bearing A549 lung cancer. Therefore, these self-assembled theranostic nanoparticles may have great potential for cancer clinical diagnosis and therapy.
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