Targeted paclitaxel nanoparticles modified with follicle-stimulating hormone β 81–95 peptide show effective antitumor activity against ovarian carcinoma

Zhang, Xiaoyan; Kang, Yu; Hong, Shanshan; Zheng, Yufang; Sun, Hong; Xu, Congjian

doi:10.1016/j.ijpharm.2013.06.038

Cited by 34 publications

(20 citation statements)

References 49 publications

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“…Gershenson et al [15] reported moderate anti-tumor activity of hormone therapy in patients with recurrent LGSC. FSHR or GnRHR targeted agents have been developed by using corresponding ligands, and phase II studies have shown their promising applications for ovarian cancer [36, 37]. The high expression levels of hormone receptors in our study indicate the potential application of the above treatment in LGSC.…”

Section: Discussionmentioning

confidence: 55%

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC)

Feng

Wen

et al. 2017

J Ovarian Res

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BackgroundThe aim of our study was to investigate the clinical features and expression levels of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC).MethodsWe retrospectively investigated the clinical features of 26 consecutive patients with LGSC who underwent primary staging or debulking surgery between April 2005 and June 2013 in our center; concomitant primary high-grade serous ovarian cancer (HGSC) patients were randomly selected at a 2:1 ratio for comparison. Tissue microarrays were constructed from the LGSC and HGSC specimens, and the expression levels of six hormone receptors in the hypothalamic pituitary-gonadal axis were analyzed by immunohistochemistry.ResultsThe median (range) age of patients with LGSC was 54 (27–77) years. According to the FIGO staging system, the cases were distributed as follows: stage I, 6 (23.1%); stage II, 0 (0%); stage III, 19 (73.1%); and stage IV, 1 (3.8%). The 2-year and 5-year overall survival rates for LGSC were 91.8% and 67.5%, respectively. The expression levels of the hormone receptors were as follows: ER, 80.8%; PR, 34.6%; AR, 53.8%; FSHR, 84.0%; LHR, 65.4%; and GnRHR, 100%. Hormone receptor-positive patients had a better prognosis compared with hormone receptor-negative patients, but the difference was not significant.ConclusionsOur study presented a higher overall survival rate and distinctive hormone receptor expression levels of LGSC patients compared with the HGSC cohort. Patients with positive hormone receptor expression tended to have a better prognosis than the corresponding hormone receptor negative patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0300-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 55%

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC)

Feng

Wen

et al. 2017

J Ovarian Res

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“…Using the FSHR-targeting strategy, a chemotherapy drug (paclitaxel, PTX) 14, 15 or a gene silencing agent (small interfering RNA, siRNA) 16 was loaded into nanoparticles which were attached to binding domains of FSH (i.e. FSH33 or FSH β 81-95).…”

Section: Introductionmentioning

confidence: 99%

PET of Follicle-Stimulating Hormone Receptor: Broad Applicability to Cancer Imaging

Hong¹,

Yan²,

Shi³

et al. 2015

Mol. Pharmaceutics

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Selective overexpression of follicle-stimulating hormone receptor (FSHR) inside the vascular endothelium of tumors has been confirmed to play critical roles in angiogenesis, tumor invasion, and metastases. The expression level of FSHR correlates strongly with the response of tumors to antiangiogenic therapies. In this study, an immunoPET tracer was developed for imaging of FSHR in different cancer types. A monoclonal antibody (FSHR-mAb) against FSHR was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and used for subsequent 64Cu-labeling. NOTA-FSHR-mAb preserved FSHR specificity/affinity, confirmed by flow cytometry measurements. 64Cu-labeling was successfully conducted with decent yields (~ 25%) and high specific activity (0.93 GBq/mg). The uptake of 64Cu-NOTA-FSHR-mAb was 3.6 ± 0.8, 13.2 ± 0.7, and 14.6 ± 0.4%ID/g in FSHR-positive CAOV-3 tumors at 4, 24, and 48 h post-injection, respectively (n = 3), significantly higher (p<0.05) than that in FSHR-negative SKOV-3 tumors (2.3 ± 1.2, 8.0 ± 0.9, and 9.1 ± 1.3 %ID/g at 4, 24, and 48 h post-injection, respectively (n = 3)) except at 4 h p.i. FSHR-relevant uptake of 64Cu-NOTA-FSHR-mAb was also readily observed in other tumor types (e.g. triple-negative breast tumor MDA-MB-231 or prostate tumor PC-3). Histology studies showed universal FSHR expression in microvasculature of these four tumor types and also prominent expression in tumor cells of CAOV-3, PC-3, and MDA-MB-231. Correlations between tumor FSHR level and uptake of 64Cu-NOTA-FSHR-mAb were witnessed in this study. FSHR-specific uptake of 64Cu-NOTA-FSHR mAb in different tumors enables its applicability for future cancer theranostic applications and simultaneously establishes FSHR as a promising clinical target for cancer.

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“…In addition, paclitaxel NPs modified with FSH β 33–53 peptide or FSH β 81–95 peptide showed a higher antitumor efficacy against ovarian cancer and produced fewer adverse side effects [8,9]. FSHR-mediated targeted therapeutics show high potential in ovarian cancer therapy because of limited FSHR distribution in the human reproductive system.…”

Section: Introductionmentioning

confidence: 99%

Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro

et al. 2013

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BackgroundRNA interference technology has shown high therapeutic potential for cancer treatment. However, serum instability, poor tissue permeability and non-specific uptake of short interfering RNA (siRNA) limit its administration in vivo. To overcome these limitations and improve the specificity for ovarian cancer, we developed a targeted nanoparticle delivery system for siRNA. This system included follicle-stimulating hormone (FSH) β 33–53 peptide as a targeting moiety that specifically recognized FSH receptor (FSHR) expressed on ovarian cancer cells. Growth regulated oncogene α (gro-α) has been reported to be involved in ovarian cancer development and progression. Thus, siRNA targeted to gro-α was used as an antitumor drug in this delivery system.MethodsFSH β 33–53 peptide-conjugated gro-α siRNA-loaded polyethylene glycol (PEG)-polyethylenimine (PEI) nanoparticles (FSH33-G-NP) were prepared and characterized by gel retardation assay and transmission electron microscopy. Particle size and zeta potential were determined. Expression of gro-α mRNA and protein was detected by real-time quantitative RT-PCR, immunocytochemistry and enzyme-linked immunosorbent assay. The proliferation, migration and invasion of the ovarian clear cell carcinoma cell line ES-2 were evaluated by cell counting kit-8 assay, cell scratch assay and transwell migration assay.ResultsA siRNA sequence that is effective in silencing gro-α expression was obtained and loaded into the targeted delivery system. Compared with gro-α siRNA-loaded nanoparticles without FSH peptide modification (G-NP), FSH33-G-NP significantly down-regulated gro-α expression in ES-2 cells at mRNA and protein levels. Consequently, the aggressive biological behaviors of ES-2 cells, including proliferation, migration and invasion, were suppressed after silencing gro-α expression, and the addition of the FSH β 33–53 peptide enhanced the suppressive effects.ConclusionsThis study indicated that a FSHR-mediated delivery system could mediate the highly selective delivery of siRNA into ovarian cancer cells and that silencing gro-α expression could be a potential choice for ovarian cancer treatment.

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Targeted paclitaxel nanoparticles modified with follicle-stimulating hormone β 81–95 peptide show effective antitumor activity against ovarian carcinoma

Cited by 34 publications

References 49 publications

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC)

Expression of hypothalamic-pituitary-gonadal axis-related hormone receptors in low-grade serous ovarian cancer (LGSC)

PET of Follicle-Stimulating Hormone Receptor: Broad Applicability to Cancer Imaging

Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro

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