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A tumoral acidic pH-responsive drug delivery system based on a novel photosensitizer (fullerene) for in vitro and in vivo chemo-photodynamic therapy

机译:基于新型光敏剂(富勒烯)的肿瘤酸性pH响应药物递送系统,用于体外和体内化学光动力疗法

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Fullerene has shown great potential both in drug delivery and photodynamic therapy. Herein, we developed a doxorubicin (DOX)-loaded poly(ethyleneimine) (PEI) derivatized fullerene (C60-PEI-DOX) to facilitate combined chemotherapy and photodynamic therapy in one system, and DOX was covalently conjugated onto C60-PEI by the pH-sensitive hydrazone linkage. The release profiles of DOX from C60-PEI-DOX showed a strong dependence on the environmental pH value. The biodistributions of C60-PEI-DOX were investigated by injecting CdSe/ZnS (Qds) labeled conjugates (C60-PEI-DOX/Qds) into tumor-bearing mice. C60-PEI-DOX/Qds showed a higher tumor targeting efficiency compared with Qds alone. Compared with free DOX in an in vivo murine tumor model, C60-PEI-DOX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its good tumor targeting efficacy and the 2.4-fold greater amount of DOX released in the tumor than in the normal tissues. C60-PEI-DOX also showed high antitumor efficacy during photodynamic therapy. The ability of C60-PEI-DOX nanoparticles to combine local specific chemotherapy with external photodynamic therapy significantly improved the therapeutic efficacy of the cancer treatment, the combined treatment demonstrating a synergistic effect. These results suggest that C60-PEI-DOX may be promising for high treatment efficacy with minimal side effects in future therapy.
机译:富勒烯在药物递送和光动力疗法中均显示出巨大潜力。本文中,我们开发了负载阿霉素(DOX)的聚(乙烯亚胺)(PEI)衍生富勒烯(C60-PEI-DOX),以促进在一个系统中进行联合化学疗法和光动力疗法,并且通过pH将DOX共价缀合至C60-PEI敏感的linkage键。 DO从C60-PEI-DOX的释放曲线显示出对环境pH值的强烈依赖性。通过将CdSe / ZnS(Qds)标记的偶联物(C60-PEI-DOX / Qds)注射到荷瘤小鼠中,研究了C60-PEI-DOX的生物分布。与单独的Qds相比,C60-PEI-DOX / Qds显示出更高的肿瘤靶向效率。与体内小鼠肿瘤模型中的游离DOX相比,C60-PEI-DOX具有良好的肿瘤靶向作用,并且在肿瘤中释放的DOX量比在体内高2.4倍,因此具有更高的抗肿瘤功效,而对正常器官没有明显的毒性作用。正常组织。 C60-PEI-DOX在光动力疗法中也显示出很高的抗肿瘤功效。 C60-PEI-DOX纳米颗粒将局部特异性化学疗法与外部光动力疗法相结合的能力显着提高了癌症治疗的疗效,这种联合治疗表现出协同作用。这些结果表明,C60-PEI-DOX有望在未来的治疗中以较高的治疗效果且副作用最小。

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