State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University , Tianjin 300071, China.
Tianjin Key Laboratory of Tumor Microenviroment and Neurovascular Regulation, School of Medicine, Nankai University , Tianjin 300071, China.
ACS Appl Mater Interfaces. 2017 Jul 12;9(27):22278-22288. doi: 10.1021/acsami.7b06105. Epub 2017 Jun 28.
The combination of multidrug chemotherapy and photothermal therapy (PTT) enhances cancer therapeutic efficacy. Herein, we develop a simple and smart pH/NIR dual-stimulus-responsive degradable mesoporous CoFeO@PDA@ZIF-8 sandwich nanocomposite. The mesoporous CoFeO core acts as T-weighted magnetic resonance (MR) imaging probe, PTT agent, and loading platform of hydrophilic doxorubicin (DOX). A polydopamine (PDA) layer is used to avoid the premature leakage of DOX before arriving at tumor site, enhance PTT efficiency, and facilitate the integration of ZIF-8 (a kind of metal-organic framework). The ZIF-8 shell serves to encapsulate hydrophobic camptothecin (CPT) and as the switch for the pH and NIR stimulation-responsive release of the two drugs. Therefore, T-weighted MR imaging-guided multidrug chemotherapy and PTT synergistic treatment is achieved. Two kinds of anticancer drugs, hydrophilic DOX and hydrophobic CPT, are successfully loaded in CoFeO and ZIF-8, respectively, so no mutual interference between the two drugs exists. A unique two-stage stepwise release process is exhibited for CPT and DOX with an interval of 12 h to improve the anticancer efficacy under the acidic microenvironment of tumor tissue. NIR irradiation achieves the burst drug-release and PTT after laser stimulation, simultaneously. With this smart design, high drug concentration is achieved at the tumor site by quick release, especially for the therapeutic drugs that show nonlinear pharmacokinetics, and PTT is integrated efficiently. Furthermore, negligible biotoxicity and a remarkable synergic antitumor effect of the hybrid nanocomposites are validated by HepG2 cells and tumor-bearing mice as models. Our multidrug delivery-releasing composite improves tumor therapeutic efficiency significantly compared with a single-drug chemotherapy system. The simple multifunctional composite system can be applied as an effective platform for personal nanomedicine with diagnosis, smart drug delivery, and cancer treatment through its remarkable photothermal property and controllable multidrug release.
多药化疗与光热治疗（PTT）的联合应用增强了癌症的治疗效果。在此，我们开发了一种简单而智能的 pH/NIR 双刺激响应可降解介孔 CoFeO@PDA@ZIF-8 夹层纳米复合材料。介孔 CoFeO 核作为 T 加权磁共振（MR）成像探针、PTT 剂和具有亲水性阿霉素（DOX）的负载平台。聚多巴胺（PDA）层用于避免 DOX 在到达肿瘤部位之前过早泄漏，提高 PTT 效率，并促进 ZIF-8（一种金属有机骨架）的整合。ZIF-8 壳用于封装疏水性喜树碱（CPT），并作为两种药物的 pH 和 NIR 刺激响应释放的开关。因此，实现了 T 加权 MR 成像引导的多药化疗和 PTT 协同治疗。亲水性 DOX 和疏水性 CPT 两种抗癌药物分别成功装载在 CoFeO 和 ZIF-8 中，因此两种药物之间不存在相互干扰。CPT 和 DOX 呈现独特的两阶段分步释放过程，间隔 12 小时，以改善肿瘤组织酸性微环境下的抗癌效果。NIR 照射在激光刺激后实现了药物的爆发式释放和 PTT。通过这种智能设计，在肿瘤部位实现了高药物浓度的快速释放，尤其是对于具有非线性药代动力学的治疗药物，并且高效地整合了 PTT。此外，以 HepG2 细胞和荷瘤小鼠为模型，验证了杂化纳米复合材料具有可忽略的生物毒性和显著的协同抗肿瘤作用。与单一药物化疗系统相比，我们的多药输送释放复合材料显著提高了肿瘤治疗效率。该多功能复合系统可作为具有诊断、智能药物输送和癌症治疗功能的有效个体化纳米医学平台，其显著的光热性能和可控的多药物释放可应用于此。
