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用于肿瘤细胞选择性发光的触发式“开/关”发光多肽碗状纳米颗粒

Triggered "On/off" Luminescent Polypeptide Bowl-Shaped Nanoparticles for Selective Lighting of Tumor Cells.

作者信息

Gao Yaning, Wang Yin, Jiang Jinhui, Wei Ping, Sun Hui

机构信息

State Key Laboratory of High-efficiency Coal Utilization and Green Chemical Engineering, School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan, 750021, China.

School of Humanities and Management, Ningxia Medical University, Yinchuan, 750004, China.

出版信息

Small. 2025 Mar;21(11):e2411432. doi: 10.1002/smll.202411432. Epub 2025 Jan 29.

DOI:10.1002/smll.202411432
PMID:39888201
Abstract

Functional polymeric nanoparticles, especially those with anisotropic structures, have shown significant potential and advantages in biomedical applications including detecting, bioimaging, antimicrobial and anticancer. Herein, tetraphenylethylene (TPE) and azobenzene modified polypeptides of poly((-glutamic acid) tetraphenylethylene-stat-(-glutamic acid)) (P(GATPE-stat-GA)) and poly((-glutamic acid) azobenzene-stat-(-glutamic acid)) (P(GAAzo-stat-GA) are synthesized, which self-assemble into bowl-shaped nanoparticles (BNPs) with controlled diameter, opening size and fluorescent property individually, or by co-assembly. Due to the quenching effect of azobenzene, the fluorescence of the coassembled BNPs is completely inhibited. Upon incubated under reduction environment, the fluorescence of the BNPs is re-excited owing to the reduction or break of azo bonds. Benefiting from the high-level azo reductase in hypoxic liver cancer cells comparing to normal liver cells, the quenched BNPs exhibit pronounced fluorescence signal in human hepatoma (HepG2) cells under hypoxic condition, demonstrating the high efficiency of the reduction-responsive luminescent BNPs for selective screening of tumor cells. In addition, it is also found that a proper opening size promotes the cellular uptake of the BNPs even with size up to micron. Overall, this study provides a fresh perspective in the controlled preparation of anisotropic polymeric nanoparticles and high efficient cancer cell screening.

摘要

功能性聚合物纳米粒子,尤其是那些具有各向异性结构的纳米粒子,在生物医学应用中已显示出巨大的潜力和优势,包括检测、生物成像、抗菌和抗癌等方面。在此,合成了四苯乙烯(TPE)和偶氮苯修饰的聚((-谷氨酸)四苯乙烯-无规-(-谷氨酸))(P(GATPE-无规-GA))和聚((-谷氨酸)偶氮苯-无规-(-谷氨酸))(P(GAAzo-无规-GA))多肽,它们分别或通过共组装自组装成具有可控直径、开口尺寸和荧光性质的碗状纳米粒子(BNPs)。由于偶氮苯的猝灭作用,共组装的BNPs的荧光被完全抑制。在还原环境下孵育时,由于偶氮键的还原或断裂,BNPs的荧光被重新激发。与正常肝细胞相比,缺氧肝癌细胞中高水平的偶氮还原酶使得猝灭的BNPs在缺氧条件下的人肝癌(HepG2)细胞中表现出明显的荧光信号,证明了还原响应发光BNPs用于选择性筛选肿瘤细胞的高效性。此外,还发现合适的开口尺寸即使在尺寸达到微米级时也能促进BNPs的细胞摄取。总体而言,本研究为各向异性聚合物纳米粒子的可控制备和高效癌细胞筛选提供了新的视角。

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