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Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells

BACKGROUND: Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into...

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Autores principales: Shi, Yijie, Su, Chang, Cui, Wenyu, Li, Hongdan, Liu, Liwei, Feng, Bo, Liu, Ming, Su, Rongjian, Zhao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219096/
https://www.ncbi.nlm.nih.gov/pubmed/25358257
http://dx.doi.org/10.1186/s12951-014-0043-7
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author Shi, Yijie
Su, Chang
Cui, Wenyu
Li, Hongdan
Liu, Liwei
Feng, Bo
Liu, Ming
Su, Rongjian
Zhao, Liang
author_facet Shi, Yijie
Su, Chang
Cui, Wenyu
Li, Hongdan
Liu, Liwei
Feng, Bo
Liu, Ming
Su, Rongjian
Zhao, Liang
author_sort Shi, Yijie
collection PubMed
description BACKGROUND: Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. RESULTS: We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-β-cyclodextrin (CM-β-CD) nanoparticles (FA-BSA-CM-β-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of −18.6 mV. FA-BSA-CM-β-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-β-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs. CONCLUSIONS: These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-β-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.
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spelling pubmed-42190962014-11-07 Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells Shi, Yijie Su, Chang Cui, Wenyu Li, Hongdan Liu, Liwei Feng, Bo Liu, Ming Su, Rongjian Zhao, Liang J Nanobiotechnology Research BACKGROUND: Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. RESULTS: We prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-β-cyclodextrin (CM-β-CD) nanoparticles (FA-BSA-CM-β-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of −18.6 mV. FA-BSA-CM-β-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-β-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs. CONCLUSIONS: These results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-β-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors. BioMed Central 2014-10-30 /pmc/articles/PMC4219096/ /pubmed/25358257 http://dx.doi.org/10.1186/s12951-014-0043-7 Text en © Shi et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Shi, Yijie
Su, Chang
Cui, Wenyu
Li, Hongdan
Liu, Liwei
Feng, Bo
Liu, Ming
Su, Rongjian
Zhao, Liang
Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
title Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
title_full Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
title_fullStr Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
title_full_unstemmed Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
title_short Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
title_sort gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-beta-cyclodextrin nanoparticles enhance drug delivery and attenuate autophagy in folate receptor-positive cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219096/
https://www.ncbi.nlm.nih.gov/pubmed/25358257
http://dx.doi.org/10.1186/s12951-014-0043-7
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