A tumor-specific cleavable nanosystem of PEG-modified C60@Au hybrid aggregates for radio frequency-controlled release, hyperthermia, photodynamic therapy and X-ray imaging.
A tumor-specific cleavable nanosystem of PEG-modified C60@Au hybrid aggregates for radio frequency-controlled release, hyperthermia, photodynamic therapy and X-ray imaging.
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DOI：
10.1016/j.actbio.2015.10.027
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发表时间：
2016
影响因子：
9.7
通讯作者：
Jinjin Shi;Zhaoyang Chen;Lei Wang;Binghua Wang;Lihua Xu;Lin Hou;Zhenzhong Zhang
中科院分区：
文献类型：
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作者：
Jinjin Shi;Zhaoyang Chen;Lei Wang;Binghua Wang;Lihua Xu;Lin Hou;Zhenzhong Zhang
利用富勒烯（C60）和金纳米粒子（AuNPs）在光动力学治疗（PDT）、药物递送和射频热治疗（RTT）等方面的潜力，通过化学沉积法将Au纳米粒子负载到C60上，并通过pH可裂解的腙键与PEG 5000进行功能化，制备了C60@Au杂化纳米复合材料。通过使C60@Au-PEG在循环过程中保持PEG在药物载体表面，而在肿瘤组织中聚集后将PEG从载体表面解离，从而将阿霉素（DOX）以很高的载药效率负载到C60@Au-PEG上。C60@Au-PEG/DOX的释放曲线显示出对射频（RF）的强烈依赖性。对于药物递送，C60@Au-PEG/DOX由于肿瘤的DOX摄取比DOX高8.6倍而提供高得多的抗肿瘤功效。此外，在本研究中，C60@Au-PEG/DOX不仅作为一种强的RTT剂用于肿瘤的射频热消融和强的光敏剂（PS）用于PDT，而且还作为一种X射线造影剂用于肿瘤诊断。在体外和体内研究中，C60@Au-PEG/DOX显示出良好的射频热光动力治疗效果、射频控制药物释放功能、肿瘤靶向性、肿瘤酸PEG解离特性和X射线成像能力，这表明C60@Au-PEG/DOX用于癌症治疗中的同时诊断和治疗。重要性声明癌症治疗中的一个重大挑战是最大限度地提高治疗效果和最小化副作用。在过去的十年里，许多纳米颗粒被用作高效药物输送的载体。然而，设计具有刺激响应控释特性、同时具有诊断和治疗功能的药物传递系统仍然是一个挑战。本研究以C60@Au-PEG/DOX为载体，构建了一种新型的药物传递系统，并探讨了其在肿瘤治疗中的应用。体外和体内实验结果表明，C60@Au-PEG/DOX通过X射线成像引导的DOX定位释放、光动力学和光热疗法，可显著提高疗效，降低全身毒性。这些结果是令人感兴趣的，因为它们证明了用于肿瘤治疗诊断应用的多功能DDS。
Taking advantages of fullerene (C60) and gold nanoparticles (AuNPs) for potentials in photodynamic therapy (PDT), drug delivery and radio frequency thermal therapy (RTT), a C60@Au hybrid nanocomposite was synthesized by chemical deposition of Au nanoparticles onto C60, and functionalized by PEG5000 via a pH cleavable hydrazone bond, making C60@Au-PEG keep the PEG on the surface of drug delivery system during circulation but dissociate PEG from the system after accumulation in tumor tissue, then doxorubicin (DOX) was loaded onto C60@Au-PEG with a very high drug loading efficiency. The release profiles of DOX from C60@Au-PEG/DOX showed strong dependences on radio frequency (RF). For the drug delivery, C60@Au-PEG/DOX afforded much higher antitumor efficacy owing to 8.6-fold higher DOX uptake of tumor than DOX. Besides, in this work, C60@Au-PEG/DOX not only served as a powerful RTT agent for RF-thermal ablation of tumor and a strong photosensitizer (PS) for PDT, but also as an X-ray contrast agent for tumor diagnosis. In thein vitroandin vivostudies, C60@Au-PEG/DOX showed excellent chemo-RF thermal-photodynamic therapeutic efficacy, RF-controlled drug releasing function, tumor targeting property, tumoral acid PEG dissociating character and X-ray imaging ability, demonstrating that there is a great potential of C60@Au-PEG/DOX for simultaneous diagnosis and therapy in cancer treatment.Statement of significanceA significant challenge in cancer therapy is to maximize the therapeutic efficacy and minimize the side effects. In the past decade, a lot of nanoparticles have been used as the carriers for efficient drug delivery. However, the design of drug delivery system (DDS) with stimuli-responsive controlled-release property, simultaneous diagnosis and therapy functions is still a challenge. Herein, we developed a new drug delivery system (C60@Au-PEG/DOX), and explored its applications in tumor therapy. Thein vitroandin vivoresults showed C60@Au-PEG/DOX could significantly improve the therapeutic efficacy and reduce the systemic toxicity through X-ray imaging guided locatable DOX release, photodynamic and photothermal therapies. These results are of interest as they demonstrate a multi-functional DDS for tumor theranostic applications.