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一种用于协同化学-磁热肿瘤治疗的pH和磁双响应水凝胶。

A pH and magnetic dual-response hydrogel for synergistic chemo-magnetic hyperthermia tumor therapy.

作者信息

Zhou Xiaohan, Wang Longchen, Xu Yanjun, Du Wenxian, Cai Xiaojun, Wang Fengjuan, Ling Yi, Chen Hangrong, Wang Zhigang, Hu Bing, Zheng Yuanyi

机构信息

Chongqing Key Laboratory of Ultrasound Molecular Imaging, State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing, The Ministry of Science and Technology, Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 PR China

Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 PR China.

出版信息

RSC Adv. 2018 Mar 8;8(18):9812-9821. doi: 10.1039/c8ra00215k. eCollection 2018 Mar 5.

Abstract

To overcome the toxicity of chemotherapy, increasing attention has been paid to local drug delivery systems (DDSs). pH-Sensitive hydrogels have emerged as promising DDS materials in the biomedical field due to their remarkable characteristics. However, the pH environment in tumor varies from person to person, which makes the applicability of systems based on pH challenging. In this study, we developed a contractible hydroxypropyl methyl cellulose (HPMC)/FeO hydrogel with dual-response pH and magnetic properties aiming to overcome the limitations of pH-sensitive hydrogel drug delivery systems and further increase their efficiency in tumor therapy. The HPMC/FeO hydrogel could act as a drug delivery system that combines pH-sensitive triggering and magnetic dual-response drug release for synergistic chemo-magnetic hyperthermia therapy. The drug delivery profile of the HPMC/FeO/doxorubicin hydrochloride (DOX) hydrogel was determined and revealed a remarkable pH-sensitive performance. After synergistic chemo-magnetic hyperthermia treatment, mice with 4T1 breast cancer xenografts recovered without any recurrence or metastasis, demonstrating the synergistic effect of chemotherapy and magnetic hyperthermia therapy. Meanwhile, reduced toxicity and superior anticancer effects were achieved due to the combined effect of the pH and magnetic hyperthermia response properties. This study demonstrated the high efficacy and low toxicity of the improved design of HPMC/FeO for drug delivery, which may provide a promising approach for the application of chemo-magnetic hyperthermia cancer therapy.

摘要

为了克服化疗的毒性,局部给药系统(DDSs)受到了越来越多的关注。pH敏感水凝胶因其显著特性已成为生物医学领域中很有前景的DDS材料。然而,肿瘤内的pH环境因人而异,这使得基于pH的系统的适用性面临挑战。在本研究中,我们开发了一种具有pH和磁双响应特性的可收缩羟丙基甲基纤维素(HPMC)/FeO水凝胶,旨在克服pH敏感水凝胶给药系统的局限性,并进一步提高其肿瘤治疗效率。HPMC/FeO水凝胶可作为一种给药系统,结合pH敏感触发和磁双响应药物释放,用于协同化学-磁热疗。测定了HPMC/FeO/盐酸阿霉素(DOX)水凝胶的药物释放曲线,结果显示出显著的pH敏感性能。在协同化学-磁热疗治疗后,4T1乳腺癌异种移植小鼠恢复且无任何复发或转移,证明了化疗和磁热疗的协同作用。同时,由于pH和磁热疗响应特性的联合作用,实现了毒性降低和抗癌效果增强。本研究证明了HPMC/FeO改进设计用于药物递送具有高效低毒特性,这可能为化学-磁热疗癌症治疗的应用提供一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d29d/9078710/725657303a8e/c8ra00215k-s1.jpg

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