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Colloids Surf B Biointerfaces. 2016 Apr 1;140:150-160. doi: 10.1016/j.colsurfb.2015.12.034. Epub 2015 Dec 23.

A study of the synergistic effect of folate-decorated polymeric micelles incorporating Hydroxycamptothecin with radiotherapy on xenografted human cervical carcinoma.

Author information

1
Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
2
Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China. Electronic address: shaozhifu513@163.com.
3
Department of Neurosurgery, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
4
Department of Nuclear Medicine, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
5
Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China. Electronic address: wjb6147@163.com.

Abstract

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 ((18)F-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.

KEYWORDS:

10-Hydroxycamptothecin; Folate; Mechanism; Micelle; Radiotherapy; Synergistic effect; Targeted drug delivery

PMID:
26752212
DOI:
10.1016/j.colsurfb.2015.12.034
[Indexed for MEDLINE]

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