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用于光热和光动力治疗的双刺激响应性多肽纳米颗粒

Dual-Stimuli-Responsive Polypeptide Nanoparticles for Photothermal and Photodynamic Therapy.

作者信息

Zhang Peiyu, Gao Zhiliang, Cui Jiwei, Hao Jingcheng

机构信息

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

出版信息

ACS Appl Bio Mater. 2020 Jan 21;3(1):561-569. doi: 10.1021/acsabm.9b00964. Epub 2019 Dec 13.

DOI:10.1021/acsabm.9b00964
PMID:35019399
Abstract

We report the assembly of dual-responsive polypeptide nanoparticles loaded with indocyanine green (ICG) using a mesoporous silica (MS) templating method for photothermal and photodynamic therapy. Polypeptide nanoparticles composed of thiol-modified polylysine (PLL) are cross-linked with disulfide bonds and modified with poly(ethylene glycol) (PEG) and pH-sheddable dimethylmaleic anhydride (DMMA), which exhibit reduction- and pH-responsiveness. Cross-linking with disulfide bonds does not influence the free amine groups on PLL chains for further cargo conjugation and surface modification. The stripped DMMA at acidic pH reverses the zeta potential of PLL nanoparticles from negative to positive charge and subsequently results in high cell association. The thermo-responsiveness and singlet oxygen generation of the loaded ICG in DMMA-modified PLL nanoparticles are comparable to those of free ICG under laser irradiation, which induces higher cytotoxicity to cancer cells compared to succinic anhydride (SA)-modified PLL nanoparticles that are not pH-responsive. The reported dual-responsive PLL nanoparticles provide a promising platform for improved photothermal and photodynamic therapy.

摘要

我们报道了一种使用介孔二氧化硅(MS)模板法制备负载吲哚菁绿(ICG)的双响应性多肽纳米颗粒,用于光热和光动力治疗。由巯基修饰的聚赖氨酸(PLL)组成的多肽纳米颗粒通过二硫键交联,并用聚乙二醇(PEG)和pH可脱落的二甲基马来酸酐(DMMA)进行修饰,表现出还原和pH响应性。通过二硫键交联不会影响PLL链上的游离胺基,以便进行进一步的货物共轭和表面修饰。在酸性pH下剥离的DMMA使PLL纳米颗粒的zeta电位从负电荷变为正电荷,随后导致高细胞结合。DMMA修饰的PLL纳米颗粒中负载的ICG在激光照射下的热响应性和单线态氧生成与游离ICG相当,与无pH响应的琥珀酸酐(SA)修饰的PLL纳米颗粒相比,对癌细胞具有更高的细胞毒性。所报道的双响应性PLL纳米颗粒为改进的光热和光动力治疗提供了一个有前景的平台。

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