Redox- and light-responsive alginate nanoparticles as effective drug carriers for combinational anticancer therapy
Redox- and light-responsive alginate nanoparticles as effective drug carriers for combinational anticancer therapy
复制标题
氧化还原和光响应型藻酸盐纳米颗粒作为联合抗癌治疗的有效药物载体
DOI：
10.1039/c7nr00005g
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发表时间：
2017
期刊：
影响因子：
6.7
通讯作者：
Kong Deling
中科院分区：
文献类型：
--
作者：
Zhang Chuangnian;Shi Gaona;Zhang Ju;Niu Jinfeng;Huang Pingsheng;Wang Zhihong;Wang Yanming;Wang Weiwei;Li Chen;Kong Deling
纳米颗粒已被广泛探索作为递送化疗剂或光敏剂以用于化疗或光动力疗法（PDT）抗癌的有效手段。在目前的工作中，脱镁叶绿酸 A (PheoA) 是一种疏水性光敏剂，通过氧化还原敏感的二硫键与藻酸盐 (PheoA-ALG) 缀合。抗癌剂阿霉素（DOX）也被负载在PheoA-ALG纳米颗粒（DOX/PheoA-ALG NPs）中，并用作联合抗肿瘤治疗的药物载体。 DOX/PheoA-ALG NP 呈球形，直径均匀，约为 210 nm。 DOX/PheoA-ALG NP 显示了氧化还原响应药物释放特性，在高谷胱甘肽水平 (10 mM) 的情况下观察到 DOX 和 PheoA 释放量加速。细胞摄取结果表明，DOX/PheoA-ALG NP 很容易被 B16 肿瘤细胞（小鼠黑色素瘤）摄取，并且与无载体药物相比，在 DOX/PheoA-ALG NP 处理的 B16 细胞中可以检测到增强的 DOX 和 PheoA 摄取。 DOX/PheoA–ALG NP 还会引发细胞内 ROS 生成，从而增强 B16 细胞的毒性。使用 B16 荷瘤小鼠的体内研究进一步表明，DOX/PheoA-ALG NPs 优先在肿瘤组织中积累，导致化疗和光动力疗法对 B16 肿瘤生长的显着抑制，这也归因于 DOX/PheoA-ALG NP 引起血清 INF-λ 水平的增加。我们的结果证明了 DOX/PheoA-ALG NP 在癌症联合治疗中的巨大潜力。
Nanoparticles have been extensively explored as effective means to deliver chemotherapeutic agents or photosensitizers for chemotherapy or photodynamic therapy (PDT) against cancer. In the present work, pheophorbide A (PheoA), a hydrophobic photosensitizer, was conjugated via a redox-sensitive disulfide linkage to alginate (PheoA–ALG). Anticancer agent, doxorubicin (DOX), was also loaded within the PheoA–ALG nanoparticles (DOX/PheoA–ALG NPs) and used as drug carriers for combinational antitumor treatment. The DOX/PheoA–ALG NPs were spherical in shape with a uniform diameter of approximately 210 nm. Redox-responsive drug releasing properties were shown by the DOX/PheoA–ALG NPs, with an accelerated amount of DOX and PheoA release observed in the presence of a high glutathione level (10 mM). Cellular uptake results showed that DOX/PheoA–ALG NPs were readily taken up by B16 tumor cells (murine melanoma) and enhanced DOX and PheoA uptake were detectable in the DOX/PheoA–ALG NPs-treated B16 cells in comparison to carrier free drugs. DOX/PheoA–ALG NPs also elicited intracellular ROS generation, which leads to enhanced toxicity in B16 cells. In vivo studies using B16 tumor-bearing mice further demonstrated that DOX/PheoA–ALG NPs were preferentially accumulated in tumor tissues, resulting in substantial inhibition of B16 tumor growth by chemotherapy and photodynamic therapy, which is also attributable to DOX/PheoA–ALG NP-elicited increase of serum INF-λ levels. Our results demonstrate a major potential of DOX/PheoA–ALG NPs for combinational cancer therapy.