Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

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Abstract

In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

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An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results.

Xavier Castellsagué, L Villa, Benjamin J. Schiller … (2008)

This review focuses on recent publications of clinical trials of two prophylactic human papillomavirus (HPV) vaccines: Gardasil (Merck & Co., Inc., Whitehouse Station, NJ USA), a quadrivalent vaccine containing L1 virus-like particles (VLPs) of types -6, 11, 16, and 18, and Cervarix (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types -16 and 18. In efficacy trials involving young women, both vaccines produced outstanding efficacy against primary and secondary endpoints associated with the vaccine type HPVs and were highly and consistently immunogenic. Both had excellent safety records and, as expected, the most frequent vaccine-related adverse were mild to moderate injection site sequelae. No evidence of waning protection was observed after four years for endpoints examined ranging from incident infection to cervical intraepithelial neoplasia grade 3 associated with the vaccine type HPVs. Gardasil was also highly efficacious at preventing vaginal/vulvar lesions and genital warts. However, neither vaccine demonstrated therapeutic efficacy against prevalent infections or lesions, regardless of the associated HPV type. Cervarix has shown limited cross-protection against infection with specific closely related types while preliminary results of limited cross-protection have been presented for Gardasil. As expected, more limited efficacy was noted for both vaccines when women with prevalent infection were included or endpoints associated with any HPV type were evaluated. Immunological bridging trials involving adolescent girls and boys were also recently published. For both vaccines, serum VLP antibody levels in girls were non-inferior to those generated in young women and antibody response to Gardasil was also non-inferior in boys. The results of these studies have led to the approval of Gardasil and Cervarix by national regulatory agencies in a number of countries.

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Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study.

Johan T. den Dunnen, Nicholas E. Sherman, P. Poll … (2002)

To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types. Population based prospective cohort study. General population in Copenhagen, Denmark. 10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions). RESULTS of cervical smear tests and cervical swabs at enrollment and at the second examination about two years later. Compared with women who were negative for human papillomavirus at enrollment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2). Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.

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The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity.

Fei Yan, Chao Zhang, Yi Zheng … (2010)

The aim of this work was to investigate the effect of triblock copolymer poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity. Docetaxel-loaded nanoparticles were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable poly(lactic-co-glycolic acid) (PLGA) with or without addition of poloxamer 188, respectively. The resulting nanoparticles were found to be spherical with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in the docetaxel-resistant MCF-7 TAX30 human breast cancer cell line could be found in comparison with that of PLGA nanoparticles. In addition, the docetaxel-loaded PLGA/poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than that of docetaxel-loaded PLGA nanoparticles and Taxotere (P < .05). In conclusion, the results showed advantages of docetaxel-loaded PLGA nanoparticles incorporated with poloxamer 188 compared with the nanoparticles without incorporation of poloxamer 188 in terms of sustainable release and efficacy in breast cancer chemotherapy. The effects of poloxamer 188, a triblock copolymer were studied on nanoparticle morphology, size, cancer cell uptake and cytotoxicity. An increased level of uptake of PLGA/poloxamer 188 nanoparticles in resistant human breast cancer cell line was demonstrated, resulting in a significantly higher level of cytotoxicity. Copyright 2010 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Limei Cai: chun513730@163.com

Rufen Yu: ydth405829@163.com

Xi Hao: heli399532@163.com

Xiangcui Ding: xiangcuidui148@hotmail.com

Journal

Journal ID (nlm-ta): Nanoscale Res Lett

Journal ID (iso-abbrev): Nanoscale Res Lett

Title: Nanoscale Research Letters

Publisher: Springer US (New York )

ISSN (Print): 1931-7573

ISSN (Electronic): 1556-276X

Publication date (Electronic): 29 August 2017

Publication date PMC-release: 29 August 2017

Publication date Collection: 2017

Volume: 12

Electronic Location Identifier: 509

Affiliations

GRID grid.452885.6, Department of Gynaecology and Obstetrics, , Ruian People’s Hospital, ; Ruian, Zhejiang 325200 China

Article

Publisher ID: 2253

DOI: 10.1186/s11671-017-2253-z

PMC ID: 5574823

PubMed ID: 28853026

SO-VID: 1fc1ee24-1672-4943-89dc-f13bec54eee3

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 26 May 2017

Date accepted : 27 July 2017

Funding

Funded by: Funding grant of Ruian People's Hospital, Ruian, China

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ScienceOpen disciplines: Nanomaterials

Keywords: genistein,cervical cancer,nanoparticles,folic acid,apoptosis

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ScienceOpen disciplines: Nanomaterials

Keywords: genistein, cervical cancer, nanoparticles, folic acid, apoptosis

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Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

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EU NanoSafety Cluster Publications: Journal Articles

Most cited references 16

An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results.

Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study.

The effect of poloxamer 188 on nanoparticle morphology, size, cancer cell uptake, and cytotoxicity.

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