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首页> 外文期刊>Advanced Functional Materials >A Smart Nanoprobe Based On Fluorescence-quenching Pegylated Nanogels Containing Gold Nanoparticles For Monitoring The Response To Cancer Therapy
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A Smart Nanoprobe Based On Fluorescence-quenching Pegylated Nanogels Containing Gold Nanoparticles For Monitoring The Response To Cancer Therapy

机译：基于荧光淬灭的含金纳米颗粒的聚乙二醇化纳米凝胶的智能纳米探针，用于监测对癌症治疗的反应

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A biocompatible, caspase-3-responsive, and fluorescence-quenching smart apoptosis nanoprobe based on a PEGylated nanogel that contains gold nanoparticles (GNPs) (fluorescence quenchers) in the cross-linked polyamine gel core and fluorescein isothiocyanate (FITC)-labeied DEVD peptides at the tethered PEG chain ends is prepared for monitoring the cancer response to therapy. FITC-DEVD-nanogel-GNP shows very little fluorescence in the absence of activated caspase-3 (normal cells) through the fluorescence resonance energy transfer (FRET) process between the GNPs and the FITC molecules, while pronounced fluorescence signals are observed in apoptotic cells because of the cleavage of the DEVD peptide by activated caspase-3 present in the cells, which results in the release of FITC molecules. Thus, remarkable quenching and dequenching of fluorescence signals in response to activated caspase-3 is observed. Apoptotic cells are detected in human hepatocyte (HuH-7) multicellular tumor spheroids (MCTSs), a commonly used three-dimensional in vitro model mimicking the in vivo biology of tumors, as early as one day post-treatment with staurosporine, an apoptosis-inducing agent; while growth inhibition (i.e., change in size) of the HuH-7 MCTSs is only observed after a delay of three days (i.e., on day 4). This demonstrates the effectiveness of the FITC-DEVD-nanogel-GNP probe as a smart nanoprobe for real-time monitoring as well as a more rapid assessment of the early response to cancer therapy.
机译：生物相容性，胱天蛋白酶3反应和荧光猝灭的智能凋亡纳米探针，基于PEG化的纳米凝胶，在交联的多胺凝胶核心和异硫氰酸荧光素（FITC）标记的DEVD肽中包含金纳米颗粒（GNP）（荧光猝灭剂）在栓系PEG链末端制备了用于监测癌症对治疗反应的药物。 FITC-DEVD-nanogel-GNP在GNP和FITC分子之间通过荧光共振能量转移（FRET）过程在缺乏激活的caspase-3（正常细胞）的情况下显示很少的荧光，而在凋亡细胞中观察到明显的荧光信号因为存在于细胞中的活化的caspase-3裂解DEVD肽，导致FITC分子的释放。因此，观察到响应于活化的caspase-3的荧光信号的显着猝灭和去猝灭。在人类肝细胞（HuH-7）多细胞肿瘤球体（MCTS）中检测到凋亡细胞，MCTS是一种常用的三维体外模型，可模拟肿瘤的体内生物学，最早在用星形孢菌素治疗后一天就可以发现，凋亡-诱导剂而HuH-7 MCTS的生长抑制（即大小改变）仅在延迟三天后（即在第4天）才能观察到。这证明了FITC-DEVD-nanogel-GNP探针作为智能纳米探针的实时监测以及对癌症治疗早期反应的更快速评估的有效性。

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