Facilely synthesized pH-responsive fluorescent polymer dots entrapping doped and coupled doxorubicin for nucleus-targeted chemotherapy
Facilely synthesized pH-responsive fluorescent polymer dots entrapping doped and coupled doxorubicin for nucleus-targeted chemotherapy
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简便合成的 pH 响应性荧光聚合物点，用于包埋掺杂和偶联的阿霉素，用于核靶向化疗
DOI：
10.1039/c7tb00394c
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发表时间：
2017
影响因子：
7
通讯作者：
Xiong Liqin
中科院分区：
文献类型：
--
作者：
Guo Yixiao;Cao Fengwen;Li Yao;Xiong Liqin
多柔比星（Dox）功能化方法可以影响纳米给药系统的Dox负载效率和释放能力。本文设计了不同的dox功能化（掺杂偶联和掺杂偶联）荧光聚（9,9-二辛基芴-邻苯并噻二唑）（PFBT）聚合物点，并对其应用性能进行了评价。采用响应性腙连接剂合成了聚乙二醇修饰的阿霉素（PEG-Dox）。采用共沉淀法自组装PEG-Dox掺杂聚合物点，并通过EDC-NHS偶联将游离的PEG-Dox偶联在聚合物点表面，制备PEG-Dox掺杂和偶联的PFBT聚合物点。PEG-Dox的腙连接体响应酸性环境，导致掺杂的Dox被释放到细胞核中，偶联的Dox改变了聚合物点的结构，加速了掺杂Dox的释放。此外，通过酰胺键连接的偶联Dox仍然在聚合物点的表面上，并且由于协同作用而保留了它们的细胞质毒性。使用PEG-Dox掺杂和偶联的PFBT聚合物点获得了很高的Dox携带效率（负载Dox的重量/ PFBT的重量）：在pH 5.5下，107%和82%的Dox在24 h内体外释放。对宫颈癌细胞（HeLa）、肺癌细胞（NCI-H292）和胶质瘤细胞（U87-MG）进行了细胞毒性和细胞成像研究；结果表明，PEG-Dox掺杂和偶联的PFBT聚合物点具有明显的杀伤效果和核靶向能力。此外，使用PEG-Dox掺杂和偶联的PFBT聚合物点，在肺荷瘤小鼠体内观察到20天的肿瘤抑制作用，没有发现体重减轻和主要器官的损伤或炎症。
Doxorubicin (Dox) functionalization methods can affect the Dox loading efficiency and release capability in nanosized drug delivery systems. Herein, different Dox-functionalized (doping, coupling, and doping and coupling) fluorescent poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT) polymer dots were designed and their application performance was evaluated. Polyethylene glycol-modified doxorubicin (PEG-Dox) was synthesized using a responsive hydrazone linker. PEG-DOX-doped polymer dots were self-assembled using a co-precipitation method and free PEG-Dox was further coupled on the surface of the polymer dots via an EDC–NHS coupling to prepare the PEG-Dox doped and coupled PFBT polymer dots. The hydrazone linker of PEG-Dox is responsive to the acidic environment, resulting in the doped Dox being released into the cell nucleus and the coupled Dox changes the structure of the polymer dots and accelerates the release of the doped Dox. Moreover, the coupled Dox linked via an amide bond was still on the surface of the polymer dots and retained their cytoplasmic toxicity for a synergistic effect. A high Dox carrying efficiency (weight of the loaded Dox/weight of PFBT) was achieved using the PEG-Dox doped and coupled PFBT polymer dots: 107% and 82% of Dox was released in vitro within 24 h at pH 5.5. The cytotoxicity and cell imaging were investigated in three cancer cell lines: cervical cancer cells (HeLa), lung cancer cells (NCI-H292), and glioma cells (U87-MG); the results indicate that the PEG-Dox doped and coupled PFBT polymer dots show a distinct killing efficacy and nucleus targeted capability. Moreover, in vivo tumor suppression was observed in lung tumor-bearing mice over 20 days and no weight loss and damage or inflammation of the major organs were detected using the PEG-Dox doped and coupled PFBT polymer dots.