College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, P. R. China.
Laoshan Laboratory, 168 Wenhai Middle Rd, Qingdao 266237, Shandong, P. R. China.
Anal Chem. 2023 Dec 19;95(50):18426-18435. doi: 10.1021/acs.analchem.3c03511. Epub 2023 Dec 5.
Non-small cell lung cancer (NSCLC) accounts for a high proportion of lung cancer cases globally, but early detection remains challenging, and insufficient oxygen supply at tumor sites leads to suboptimal treatment outcomes. Therefore, the development of core-shell Au@Pt-Se nanoprobes (Au@Pt-Se NPs) with peptide chains linked through Pt-Se bonds was designed and synthesized for NSCLC biomarker protein calcium-activated neutral protease 2 (CAPN2) and photothermal therapy (PTT) enhancement. The NP can be specifically cleaved by CAPN2, resulting in fluorescence recovery to realize the detection. The Pt-Se bonds exhibit excellent resistance to biologically abundant thiols such as glutathione, thus avoiding "false-positive" results and enabling precise detection of NSCLC. Additionally, the platinum (Pt) shell possesses catalase-like properties that catalyze the generation of oxygen from endogenous hydrogen peroxide within the tumor, thereby reducing hypoxia-inducible factor-1α (HIF-1α) levels and alleviating the hypoxic environment at the tumor site. The Au@Pt-Se NPs exhibit strong absorption bands, enabling the possibility of PTT in the near-infrared II region (NIR II). This study presents an effective approach for the early detection of NSCLC while also serving as an oxygen supplier to alleviate the hypoxic environment and enhance NIR II PTT.
非小细胞肺癌（NSCLC）在全球范围内占肺癌病例的很大比例，但早期检测仍然具有挑战性，且肿瘤部位供氧不足导致治疗效果不佳。因此，设计并合成了具有肽链通过 Pt-Se 键连接的核壳型 Au@Pt-Se 纳米探针（Au@Pt-Se NPs）用于 NSCLC 生物标志物钙激活中性蛋白酶 2（CAPN2）和光热治疗（PTT）增强。NP 可被 CAPN2 特异性切割，导致荧光恢复，从而实现检测。Pt-Se 键对生物丰富的硫醇（如谷胱甘肽）具有优异的抗性，从而避免“假阳性”结果，实现对 NSCLC 的精确检测。此外，铂（Pt）壳具有类过氧化氢酶的特性，可催化肿瘤内内源性过氧化氢产生氧气，从而降低缺氧诱导因子-1α（HIF-1α）水平并减轻肿瘤部位的缺氧环境。Au@Pt-Se NPs 具有较强的吸收带，使其有可能在近红外二区（NIR II）进行 PTT。本研究为 NSCLC 的早期检测提供了一种有效的方法，同时作为供氧剂缓解缺氧环境并增强 NIR II PTT。
