Department of IT Convergence, Korea National University of Transportation, Chungju, 380-702, Republic of Korea.
Department of Chemical & Biological Engineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea.
ChemMedChem. 2018 Nov 20;13(22):2437-2447. doi: 10.1002/cmdc.201800538. Epub 2018 Nov 5.
In the present study, a pH/redox-responsive cationic polymer dot (CD) was successfully prepared for a near-infrared (NIR)-mediated, simultaneously controllable photothermal temperature guided imaging off/on system to monitor therapeutic delivery. Carbonized disulfide cross-linked branched polyethyleneimine (bPEI) was conjugated with folic acid (FA) as a targeting moiety and partially formed an ionic complex with anionic indocyanine green (ICG) to afford a bPEI-based CD (ICG-CD). This was responsive to mild reductive (glutathione, GSH) and acidic tumor conditions, which enabled the simultaneous biodegradation of those hydrophobic and complex sites. The ICG-CD internalized readily into the cytoplasm of cancer cells by a FA receptor and cationic-mediated endocytosis in the off state, whereas if ICG-CD met intracellular GSH at high concentrations, GSH contributed partially to the recovery of fluorescence and was then internalized into acidic endosomes to induce complete restoration of fluorescence. This tumor-sensitive degradability of the CD not only facilitated ICG release in the tumor location but also allowed controllable photothermal therapy effects of nanoparticles under NIR irradiation, which resulted in improved cancer therapy. Taken together, the results indicate great potential in tumor targeting, intracellular imaging, and controllable therapeutic delivery through a fluorescence off/on assay under the pH/redox conditions of cancer cells.
在本研究中，成功制备了一种 pH/氧化还原响应性阳离子聚合物点（CD），用于近红外（NIR）介导的、同时可控的光热温度引导成像开/关系统，以监测治疗药物的递送。碳化二硫交联支化聚乙烯亚胺（bPEI）与叶酸（FA）偶联作为靶向部分，并与阴离子吲哚菁绿（ICG）部分形成离子复合物，得到基于 bPEI 的 CD（ICG-CD）。它对温和的还原（谷胱甘肽，GSH）和酸性肿瘤条件有响应，这使得那些疏水性和复杂的部位能够同时进行生物降解。在关闭状态下，FA 受体和阳离子介导的内吞作用使 ICG-CD 很容易被内化到癌细胞的细胞质中，而如果 ICG-CD 在高浓度下遇到细胞内的 GSH，GSH 部分有助于恢复荧光，然后被内化到酸性内涵体中，以诱导荧光的完全恢复。CD 的这种肿瘤敏感的降解性不仅促进了肿瘤部位的 ICG 释放，而且还允许在近红外辐射下对纳米粒子进行可控的光热治疗效应，从而提高了癌症治疗效果。总之，这些结果表明，在癌细胞的 pH/氧化还原条件下，通过荧光开/关测定，该 CD 在肿瘤靶向、细胞内成像和可控治疗药物递送方面具有很大的潜力。
