Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy

Chun-Ying Qu,1,* Min Zhou,1,* Ying-wei Chen,2 Mei-mei Chen,3 Feng Shen,1 Lei-Ming Xu11Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Gastroen...

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Autores principales: Qu CY, Zhou M, Chen YW, Chen MM, Shen F, Xu LM
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:8b44e26a636e40439075151edfddb4f72021-12-02T07:46:16ZEngineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy1178-2013https://doaj.org/article/8b44e26a636e40439075151edfddb4f72015-06-01T00:00:00Zhttp://www.dovepress.com/engineering-of-lipid-prodrug-based-hyaluronic-acid-decorated-nanostruc-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chun-Ying Qu,1,* Min Zhou,1,* Ying-wei Chen,2 Mei-mei Chen,3 Feng Shen,1 Lei-Ming Xu11Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, People’s Republic of China; 3Digestive Department, Xinhua Hospital, School of medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: The first-line chemotherapy treatment protocol for gastric cancer is combination chemotherapy of 5-fluorouracil (5-FU) and cisplatin (CDDP). The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC) platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity.Methods: First, 5-FU-stearic acid lipid conjugate was synthesized by two steps. Second, 5-FU-stearic acid prodrug and CDDP were loaded in NLC. Finally, hyaluronic acid (HA) was coated onto NLC surface. Average size, zeta potential, and drug loading capacity of NLC were evaluated. Human gastric cancer cell line BGC823 (BGC823 cells) was used for the testing of in vitro cytotoxicity assays. In vivo antitumor activity of NLC was evaluated in mice bearing BGC823 cells model.Results: HA-coated 5-FU-stearic acid prodrug and CDDP-loaded NLC (HA-FU/C-NLC) showed a synergistic effect in combination therapy and displayed the greatest antitumor activity than all of the free drugs or uncoated NLC in vitro and in vivo.Conclusion: This work reveals that HA-coated NLC could be used as a novel carrier to codeliver 5-FU and CDDP for gastric cancer therapy. HA-FU/C-NLC could be a promising targeted and combinational therapy in nanomedicine.Keywords: gastric cancer, nanostructured lipid carriers, hyaluronic acid, combination chemotherapy, lipid prodrugQu CYZhou MChen YWChen MMShen FXu LMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3911-3920 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Qu CY
Zhou M
Chen YW
Chen MM
Shen F
Xu LM
Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
description Chun-Ying Qu,1,* Min Zhou,1,* Ying-wei Chen,2 Mei-mei Chen,3 Feng Shen,1 Lei-Ming Xu11Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, People’s Republic of China; 3Digestive Department, Xinhua Hospital, School of medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: The first-line chemotherapy treatment protocol for gastric cancer is combination chemotherapy of 5-fluorouracil (5-FU) and cisplatin (CDDP). The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC) platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity.Methods: First, 5-FU-stearic acid lipid conjugate was synthesized by two steps. Second, 5-FU-stearic acid prodrug and CDDP were loaded in NLC. Finally, hyaluronic acid (HA) was coated onto NLC surface. Average size, zeta potential, and drug loading capacity of NLC were evaluated. Human gastric cancer cell line BGC823 (BGC823 cells) was used for the testing of in vitro cytotoxicity assays. In vivo antitumor activity of NLC was evaluated in mice bearing BGC823 cells model.Results: HA-coated 5-FU-stearic acid prodrug and CDDP-loaded NLC (HA-FU/C-NLC) showed a synergistic effect in combination therapy and displayed the greatest antitumor activity than all of the free drugs or uncoated NLC in vitro and in vivo.Conclusion: This work reveals that HA-coated NLC could be used as a novel carrier to codeliver 5-FU and CDDP for gastric cancer therapy. HA-FU/C-NLC could be a promising targeted and combinational therapy in nanomedicine.Keywords: gastric cancer, nanostructured lipid carriers, hyaluronic acid, combination chemotherapy, lipid prodrug
format article
author Qu CY
Zhou M
Chen YW
Chen MM
Shen F
Xu LM
author_facet Qu CY
Zhou M
Chen YW
Chen MM
Shen F
Xu LM
author_sort Qu CY
title Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
title_short Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
title_full Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
title_fullStr Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
title_full_unstemmed Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
title_sort engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/8b44e26a636e40439075151edfddb4f7
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