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用模拟化疗栓塞的低分子量肽凝胶替代经皮乙醇注射用于癌症治疗。

Substitution of Percutaneous Ethanol Injection with a Low Molecular Weight Peptide Gel Mimicking Chemoembolization for Cancer Therapy.

作者信息

Xu Long, Liang Yan, Sun Changzheng, Hao Na, Yan Jianqin, Gao Wenxia, He Bin

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325027, China.

出版信息

Nanotheranostics. 2017 Jul 6;1(3):313-325. doi: 10.7150/ntno.20468. eCollection 2017.

Abstract

In order to avoid the instability and quick separation between emulsifier and drug in the interventional chemoembolization, an injectable low molecular weight peptide gel (LMWG) was prepared to localize ethanol and chemotherapeutic for synergistic therapy. The formation mechanism, rheological property and morphology of the LMWG were investigated by NMR, UV-vis, MS and SEM. The interaction between gelator and anticancer drug doxorubicin hydrochloride (DOX) was evaluated by fluorescence spectroscopy and its contribution on drug loading properties was demonstrated. The gel was non-toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. DOX as well as ethanol were encapsulated in the gel and injected in breast cancer bearing mice with low drug dose (2.5 mg/kg body weight). The LMWG surrounded tumors act as a depot for ethanol release and release DOX to induce the apoptosis of cancer cells. With the combination of percutaneous ethanol injection (PEI) and chemotherapy, the DOX loaded LMWG exhibited great significance in necrosis of tumor tissue and exciting tumor inhibition efficiency.

摘要

为避免介入性化疗栓塞中乳化剂与药物之间的不稳定性和快速分离,制备了一种可注射的低分子量肽凝胶(LMWG),用于定位乙醇和化疗药物以进行协同治疗。通过核磁共振(NMR)、紫外可见光谱(UV-vis)、质谱(MS)和扫描电子显微镜(SEM)研究了LMWG的形成机制、流变学性质和形态。通过荧光光谱评估了凝胶剂与抗癌药物盐酸多柔比星(DOX)之间的相互作用,并证明了其对药物负载性能的贡献。该凝胶对3T3成纤维细胞和4T1乳腺癌细胞均无毒。DOX和乙醇被包裹在凝胶中,并以低药物剂量(2.5mg/kg体重)注射到荷乳腺癌小鼠体内。包围肿瘤的LMWG作为乙醇释放的储存库,并释放DOX以诱导癌细胞凋亡。通过经皮乙醇注射(PEI)和化疗相结合,负载DOX的LMWG在肿瘤组织坏死和显著的肿瘤抑制效率方面具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3984/5646736/d6b564df3dd7/ntnov01p0313g001.jpg

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