Preparation of photo-controlled release ROS-responsive Ce6/elemene co-loaded liposomes and study on the effect on enhancing apoptosis of NMIBC.

Xiulin Zhang, Wei Mei, Dongyan Guo, Jing Sun, Yajun Shi, Xiaofei Zhang, Junbo Zou, Jiangxue Cheng, Fei Luan, Bingtao Zhai, Huan Tian
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Abstract

At present, chemotherapy combined with photodynamic therapy is exerting satisfactory therapeutic effects in the treatment of tumors. Chlorin e6 (Ce6) is a photosensitizer with high efficiency and low dark toxicity. At the same time, elemene (ELE) contains high-efficiency and low-toxicity anti-cancer active ingredients, which can effectively penetrate tumor tissue and inhibit its recovery and proliferation. Due to the poor water solubility of these two drugs, we prepared ELE/Ce6 co-loaded liposomes (Lipo-ELE/Ce6) to improve their water solubility, thereby enhancing the anti-tumor effect. The characterization of Lipo-ELE/Ce6 showed that Lipo-ELE/Ce6 had suitable encapsulation efficiency (EE), particle size, polydispersity (PDI), zeta potential, and good photo-controlled release properties. In vitro, Lipo-ELE/Ce6 effectively inhibited the growth of T24 cells and induced apoptosis, and more importantly, in vivo experiments showed that Lipo-ELE/Ce6 had significant anti-tumor effects, which was significantly better than free drugs. The above results suggest that Lipo-ELE/Ce6 can significantly enhance the induction of apoptosis of non-muscle invasive bladder cancer (NMIBC) by light-controlled release and ROS response.

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制备光控释放 ROS 响应的 Ce6/elemene 共载脂质体并研究其对增强 NMIBC 细胞凋亡的作用。
目前,化疗结合光动力疗法在治疗肿瘤方面取得了令人满意的疗效。氯素 e6(Ce6)是一种高效、低暗毒性的光敏剂。同时,榄香烯(ELE)含有高效低毒的抗癌活性成分,能有效渗透肿瘤组织,抑制肿瘤的恢复和增殖。由于这两种药物的水溶性较差,我们制备了ELE/Ce6共载脂质体(Lipo-ELE/Ce6),以提高其水溶性,从而增强抗肿瘤效果。Lipo-ELE/Ce6的表征结果表明,Lipo-ELE/Ce6具有合适的包封效率(EE)、粒度、多分散性(PDI)、Zeta电位和良好的光控释放特性。体外实验表明,Lipo-ELE/Ce6能有效抑制T24细胞的生长并诱导细胞凋亡,更重要的是,体内实验表明,Lipo-ELE/Ce6具有显著的抗肿瘤作用,明显优于游离药物。上述结果表明,Lipo-ELE/Ce6 可通过光控释放和 ROS 反应显著增强非肌层浸润性膀胱癌(NMIBC)的细胞凋亡诱导作用。
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