title: A study of the synergistic effect of folate-decorated polymeric micelles incorporating Hydroxycamptothecin with radiotherapy on xenografted human cervical carcinoma.
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.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China. Electronic address: shaozhifu513@163.com.
authors.forename: ShaoZhi
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: XingHu
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: YanXin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: GuangPeng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: XiaoYang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Nuclear Medicine, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Sichuan Medical University, Luzhou 646000, China. Electronic address: wjb6147@163.com.
authors.forename: JingBo
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D019788:Fluorodeoxyglucose F18; D005492:Folic Acid / Q000737:chemistry*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C468783:H2AX protein, human; D006657:Histones; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C527042:hydroxycamptothecinum; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D019788:Fluorodeoxyglucose F18; D011092:Polyethylene Glycols; D005492:Folic Acid; D002166:Camptothecin
keywords: 10-Hydroxycamptothecin; Folate; Mechanism; Micelle; Radiotherapy; Synergistic effect; Targeted drug delivery