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Site-Selective in Situ Growth-Induced Self-Assembly of Protein–Polymer Conjugates into pH-Responsive Micelles for Tumor Microenvironment Triggered Fluorescence Imaging
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-10-23 00:00:00 , DOI: 10.1021/acs.biomac.8b01368 Pengyong Li 1 , Mengmeng Sun 1 , Zhikun Xu 1 , Xinyu Liu 1 , Wenguo Zhao 1 , Weiping Gao 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-10-23 00:00:00 , DOI: 10.1021/acs.biomac.8b01368 Pengyong Li 1 , Mengmeng Sun 1 , Zhikun Xu 1 , Xinyu Liu 1 , Wenguo Zhao 1 , Weiping Gao 1
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Self-assembly of site-selective protein–polymer conjugates into stimuli-responsive micelles is interesting owing to their potential biomedical applications, ranging from molecular imaging to drug delivery, but remains a significant challenge. Herein we report a method of site-selective in situ growth-induced self-assembly (SIGS) to synthesize site-specific human serum albumin-poly(2-(diisopropylamino)ethyl methacrylate) (HSA-PDPA) conjugates that can in situ self-assemble into pH-responsive micelles with tunable morphologies. Indocyanine green (ICG) was selectively loaded into the core of sphere-like HSA-PDPA micelles to form pH-responsive fluorescence nanoprobes. The nanoprobes rapidly dissociated into protonated individual unimers at a transition pH of around 6.5, that is the extracellular pH of tumors, which resulted in a sharp fluorescence increase and markedly enhanced cellular uptake. In a tumor-bearing mouse model, they exhibited greatly enhanced tumor fluorescence imaging as compared to ICG alone and pH-nonresponsive nanoprobes. These findings suggest that pH-responsive and site-selective protein–polymer conjugate micelles synthesized by SIGS are promising as a new class of tumor microenvironment-responsive nanocarriers for enhanced tumor imaging and therapy.
中文翻译：
站点选择性原位生长诱导的蛋白质-聚合物自组装缀合为肿瘤微环境触发的荧光成像的pH响应胶束。
将位点选择性蛋白质-聚合物缀合物自组装成刺激反应性胶束很有趣，这是因为它们具有潜在的生物医学应用（从分子成像到药物递送），但仍然是一个巨大的挑战。本文中，我们报告了一种位点选择性原位生长诱导的自组装（SIGS）方法，可以合成可以原位自我定位的位点特异性人血清白蛋白-聚（2-（二异丙基氨基）甲基丙烯酸乙酯）（HSA-PDPA）共轭物-组装成具有可调形态的pH响应胶束。将吲哚菁绿（ICG）选择性地加载到球状HSA-PDPA胶束的核心中，以形成pH响应荧光纳米探针。纳米探针在大约6.5的过渡pH（即肿瘤的细胞外pH）下迅速分解成质子化的单个单体。导致荧光急剧增加并显着增强细胞摄取。在荷瘤小鼠模型中，与单独使用ICG和无pH响应的纳米探针相比，它们显示出大大增强的肿瘤荧光成像。这些发现表明，SIGS合成的pH响应性和位点选择性蛋白聚合物共轭胶束有望作为一类新型的肿瘤微环境响应性纳米载体，用于增强肿瘤的成像和治疗。
更新日期：2018-10-23
中文翻译：
站点选择性原位生长诱导的蛋白质-聚合物自组装缀合为肿瘤微环境触发的荧光成像的pH响应胶束。
将位点选择性蛋白质-聚合物缀合物自组装成刺激反应性胶束很有趣，这是因为它们具有潜在的生物医学应用（从分子成像到药物递送），但仍然是一个巨大的挑战。本文中，我们报告了一种位点选择性原位生长诱导的自组装（SIGS）方法，可以合成可以原位自我定位的位点特异性人血清白蛋白-聚（2-（二异丙基氨基）甲基丙烯酸乙酯）（HSA-PDPA）共轭物-组装成具有可调形态的pH响应胶束。将吲哚菁绿（ICG）选择性地加载到球状HSA-PDPA胶束的核心中，以形成pH响应荧光纳米探针。纳米探针在大约6.5的过渡pH（即肿瘤的细胞外pH）下迅速分解成质子化的单个单体。导致荧光急剧增加并显着增强细胞摄取。在荷瘤小鼠模型中，与单独使用ICG和无pH响应的纳米探针相比，它们显示出大大增强的肿瘤荧光成像。这些发现表明，SIGS合成的pH响应性和位点选择性蛋白聚合物共轭胶束有望作为一类新型的肿瘤微环境响应性纳米载体，用于增强肿瘤的成像和治疗。
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