Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation

Kai Liu,1 Zhi-qi Wang,2 Shi-jiang Wang,3 Ping Liu,4 Yue-hong Qin,5 Yan Ma,3 Xiao-Chen Li,6 Zhi-Jun Huo7 1Department of Gastrointestinal Surgery, 2Department of Head and Neck Surgery, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 4Department of Pharmacy, 5Department of Ne...

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Autores principales:	Liu K, Wang ZQ, Wang SJ, Liu P, Qin YH, Ma Y, Li XC, Huo ZJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/db7936e0d9504194a4d8c5a1aa470440
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spelling	oai:doaj.org-article:db7936e0d9504194a4d8c5a1aa4704402021-12-02T11:01:35ZHyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation1178-2013https://doaj.org/article/db7936e0d9504194a4d8c5a1aa4704402015-10-01T00:00:00Zhttps://www.dovepress.com/hyaluronic-acid-tagged-silica-nanoparticles-in-colon-cancer-therapy-th-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kai Liu,1 Zhi-qi Wang,2 Shi-jiang Wang,3 Ping Liu,4 Yue-hong Qin,5 Yan Ma,3 Xiao-Chen Li,6 Zhi-Jun Huo7 1Department of Gastrointestinal Surgery, 2Department of Head and Neck Surgery, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 4Department of Pharmacy, 5Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, 6Department of Internal Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, 7Department of Breast Disease Center, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Abstract: Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy. Keywords: colon cancer, 5-fluorouracil, nanoparticles, hyaluronic acid, apoptosisLiu KWang ZQWang SJLiu PQin YHMa YLi XCHuo ZJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6445-6454 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Liu K Wang ZQ Wang SJ Liu P Qin YH Ma Y Li XC Huo ZJ Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
description	Kai Liu,1 Zhi-qi Wang,2 Shi-jiang Wang,3 Ping Liu,4 Yue-hong Qin,5 Yan Ma,3 Xiao-Chen Li,6 Zhi-Jun Huo7 1Department of Gastrointestinal Surgery, 2Department of Head and Neck Surgery, 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, 4Department of Pharmacy, 5Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, 6Department of Internal Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, 7Department of Breast Disease Center, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China Abstract: Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy. Keywords: colon cancer, 5-fluorouracil, nanoparticles, hyaluronic acid, apoptosis
format	article
author	Liu K Wang ZQ Wang SJ Liu P Qin YH Ma Y Li XC Huo ZJ
author_facet	Liu K Wang ZQ Wang SJ Liu P Qin YH Ma Y Li XC Huo ZJ
author_sort	Liu K
title	Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
title_short	Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
title_full	Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
title_fullStr	Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
title_full_unstemmed	Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
title_sort	hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/db7936e0d9504194a4d8c5a1aa470440
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Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation

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