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90Plus Zeta測量應用案例-2016-15
閱讀：348 發布時間：2016-5-26文獻名： A study of the synergistic effect of folate-decorated polymeric micelles incorporating Hydroxycamptothecin with radiotherapy on xenografted human cervical carcinoma
作者： Hong Youa, ShaoZhi Fua, XingHu Qinb, YanXin Yua, Bo Yanga, GuangPeng Zhanga, XiaoYang Suna, Yue Fengc, Yue Chenc, JingBo Wua
a Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China
b Department of Neurosurgery, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China
c Department of Nuclear Medicine, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China
摘要：In this study, Hydroxycamptothecin (HCPT)-loaded micelles were formed in water by the self-assembly of folate (FA)-decorated amphiphilic block copolymer, methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL), and achieved a hydrodynamic diameter about of 132 nm. HCPT release from the micelles exhibited no initial burst but showed a sustained release profile. The cytotoxicity and targeting ability of FA conjugated polymeric micelles was investigated by using methylthiazoletetrazolium (MTT) and fluorescence microscopy. We found that FA-conjugated micelles had superior cytotoxicity against HeLa cells compared to non-conjugated micelles, and that they exerted this effect by folate receptor (FR)-mediated endocytosis. In addition, HeLa cells were xenografted into nude mice and subjected to radiotherapy (RT) and/or HCPT-loaded micelle treatment. The antitumor efficacy was detected by analysis of tumor growth delay (TGD) and median survival time. Micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) was performed to assess early tumor response to HCPT-loaded micelles in combination with RT. Analysis of cell cycle redistribution, apoptosis and expression of histone H2AX phosphorylation (λ-H2AX) was used to evaluate the mechanism by which HCPT loaded micelles led to radiosensitization. Taken together, the results showed that HCPT-loaded FA decorated micelles efficiently sensitized xenografts in mice to RT, and induced G2/M phase arrest, apoptosis and expression of λ-H2AX.
關鍵詞：Radiotherapy; 10-Hydroxycamptothecin; Micelle; Folate; Targeted drug delivery; Synergistic effect; Mechanism