pH and glutathione dual-triggered supramolecular assemblies as synergistic and controlled drug release carriers
pH and glutathione dual-triggered supramolecular assemblies as synergistic and controlled drug release carriers
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pH和谷胱甘肽双触发超分子组装体作为协同和控制药物释放载体
DOI：
10.1039/c7py01644a
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发表时间：
2017-12-14
影响因子：
4.6
通讯作者：
Li, Bang-Jing
中科院分区：
文献类型：
--
作者：
Kang, Yang;Ju, Xin;Li, Bang-Jing
通过喜树碱（CPT）上的金刚烷（ADA）和透明质酸（HA）侧链上的β-环糊精（β-CD）之间的非共价主客体相互作用，构建了pH和谷胱甘肽（GSH）双重生物相关触发超分子体系。所获得的非共价超分子beta-CD-g-OX-HA/ADA-CPT复合物在细胞外环境中可进一步自组装成具有恒定载药量的稳定均匀的球形胶束结构，但由于酸性环境和高浓度GSH的存在，在癌细胞的胞质溶胶中被裂解，导致协同快速的pH和GSH触发的药物释放行为。以Hep G2癌细胞为模型，MTT法检测了超分子beta-CD-g-OX-HA/ADA-CPT胶束的细胞毒性，结果表明，与游离CPT相比，超分子beta-CD-g-OX-HA/ADA-CPT胶束对Hep G2癌细胞的增殖抑制作用增强，且beta-CD-g-OX-HA具有良好的细胞相容性。β-CD-g-OX-HA/ADA-CPT胶束的体内研究显示出更高的体内功效而没有副作用，并且还证实了β-CD-g-OX-HA的相容性。预计这种超分子复合物将有可能制造用于癌症治疗的新型生物相关触发纳米载体。
A pH and glutathione (GSH) dual bio-relevant triggered supramolecular system is constructed through the non-covalent host-guest interactions between the adamantane (ADA) on camptothecin (CPT) and beta-cyclodextrin (beta-CD) on the side chain of the backbone of hyaluronic acid (HA). The obtained non-covalent supramolecular beta-CD-g-OX-HA/ADA-CPT complex could further self-assemble into a stable uniform sphere micellar structure with constant drug loading content in the extracellular environment but is cleaved in the cytosol of the cancer cells due to the acidic environment and the presence of a high concentration of GSH, resulting in a synergistic-fast pH and GSH triggered drug releasing behavior. The cytotoxicity of the supramolecular beta-CD-g-OX-HA/ADA-CPT micelles was investigated using Hep G2 cancer cells by MTT assays, which displayed that supramolecular beta-CD-g-OX-HA/ADA-CPT micelles had exhibited enhanced cellular proliferation inhibition against Hep G2 cancer cells compared to the free CPT, while the beta-CD-g-OX-HA had good cell compatibility. In vivo studies of the beta-CD-g-OX-HA/ADA-CPT micelles showed a higher in vivo efficacy without side effects and also confirmed the compatibility of the beta-CD-g-OX-HA. It is anticipated that this supramolecular complex will give the possibility to fabricate new types of bio-relevant triggered nanocarriers for cancer therapy.