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90Plus Zeta測量應(yīng)用案例-2016-15

閱讀:339          發(fā)布時間:2016-5-26

文獻(xiàn)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(guān)鍵詞:Radiotherapy; 10-Hydroxycamptothecin; Micelle; Folate; Targeted drug delivery; Synergistic effect; Mechanism
 

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