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负载PM1的重组人H-铁蛋白纳米笼:一种用于识别癌细胞的新型pH响应传感平台。

PM1-loaded recombinant human H-ferritin nanocages: A novel pH-responsive sensing platform for the identification of cancer cells.

作者信息

Xia Xiaoyu, Tan Xiaoyi, Wu Chao, Li Yao, Zhao Guanghua, Du Ming

机构信息

School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

出版信息

Int J Biol Macromol. 2022 Feb 28;199:223-233. doi: 10.1016/j.ijbiomac.2021.12.068. Epub 2021 Dec 28.

DOI:10.1016/j.ijbiomac.2021.12.068
PMID:34971641
Abstract

The aggregation-induced emission (AIE) material has been widely used in biological detection due to their unique property of fluorescing in aggregation state. However, the poor dispersion and biocompatibility limit its application in in vivo real-time imaging. Here, a novel strategy is designed to obtain pH-responsive AIE nanomaterials, working through 4-Undecoxy Tetraphenyl Ethylene Methacrylate (PM1) block, with excellent features (dispersion, biocompatibility, self-reconstruction and cancer specific recognition). The recombinant human H-ferritin (rHuHF) was used to prepare rHuHF-PM1 nanocomposites which effectively supported the dispersion and transfer of PM1 in the biological environment, even making it target tumor cells due to the overexpression of ferritin receptors on tumor cells. To simulate the changes of rHuHF in intracellular lysosomes, particle size and fluorescence of rHuHF-PM1 were analyzed, which reflected the loose structural changes of rHuHF nanocages in weak acid system that facilitated the degradation of macromolecular rHuHF in intracellular lysosomes and following release of PM1. The released PM1 molecules aggregated and emitted brilliant blue fluorescence. Several cell lines, Hela, HT-29, HepG2, L-O2 and HUVEC have all been sensitively detected and distinguished. Accordingly, this nanocage has a potential to be applied to disease diagnosis and provides a novel sensing platform for the identification of cancer.

摘要

聚集诱导发光(AIE)材料因其在聚集态下发光的独特性质而被广泛应用于生物检测。然而,其较差的分散性和生物相容性限制了它在体内实时成像中的应用。在此,设计了一种新策略来获得pH响应性AIE纳米材料,该材料通过4-十一烷氧基甲基丙烯酸四苯乙烯酯(PM1)嵌段起作用,具有优异的特性(分散性、生物相容性、自我重构和癌症特异性识别)。重组人H-铁蛋白(rHuHF)被用于制备rHuHF-PM1纳米复合材料,该复合材料有效地支持了PM1在生物环境中的分散和转运,甚至由于肿瘤细胞上铁蛋白受体的过表达而使其靶向肿瘤细胞。为了模拟rHuHF在细胞内溶酶体中的变化,分析了rHuHF-PM1的粒径和荧光,这反映了rHuHF纳米笼在弱酸体系中的结构松散变化,促进了细胞内溶酶体中大分子rHuHF的降解以及随后PM1的释放。释放出的PM1分子聚集并发出明亮的蓝色荧光。对几种细胞系,包括Hela、HT-29、HepG2、L-O2和HUVEC都进行了灵敏的检测和区分。因此,这种纳米笼具有应用于疾病诊断的潜力,并为癌症识别提供了一个新型传感平台。

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