In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system

In this study, we modulated the anti-cancer efficacy of 5-Fluorouracil (5-FU) using a carrier system with enhanced targeting efficacy towards folate receptors (FRs) expressing malignant tissues. The 5-FU drug was loaded onto Mn-ZnS quantum dots (QDs) encapsulated with chitosan (CS) biopolymer and co...

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Main Authors: Bwatanglang, Ibrahim Birma, Faruq, Mohammad, Yusof, Nor Azah, Abdullah, Jaafar, Mohammed Alitheen, Noorjahan Banu, Hussein, Mohd Zubir, Abu, Nadiah, Mohamad, Nurul Elyani, Nordin, Noraini, Zamberi, Nur Rizi, Yeap, Swee Keong
Format: Article
Language:English
Published: Elsevier 2016
Online Access:http://psasir.upm.edu.my/id/eprint/56587/
http://psasir.upm.edu.my/id/eprint/56587/1/In%20vivo%20tumor%20targeting%20and%20anti-tumor%20effects%20of%205-fluororacil%20loaded%2C%20folic%20acid%20targeted%20quantum%20dot%20system.pdf
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author Bwatanglang, Ibrahim Birma
Faruq, Mohammad
Yusof, Nor Azah
Abdullah, Jaafar
Mohammed Alitheen, Noorjahan Banu
Hussein, Mohd Zubir
Abu, Nadiah
Mohamad, Nurul Elyani
Nordin, Noraini
Zamberi, Nur Rizi
Yeap, Swee Keong
author_facet Bwatanglang, Ibrahim Birma
Faruq, Mohammad
Yusof, Nor Azah
Abdullah, Jaafar
Mohammed Alitheen, Noorjahan Banu
Hussein, Mohd Zubir
Abu, Nadiah
Mohamad, Nurul Elyani
Nordin, Noraini
Zamberi, Nur Rizi
Yeap, Swee Keong
author_sort Bwatanglang, Ibrahim Birma
building UPM Institutional Repository
collection Online Access
description In this study, we modulated the anti-cancer efficacy of 5-Fluorouracil (5-FU) using a carrier system with enhanced targeting efficacy towards folate receptors (FRs) expressing malignant tissues. The 5-FU drug was loaded onto Mn-ZnS quantum dots (QDs) encapsulated with chitosan (CS) biopolymer and conjugated with folic acid (FA) based on a simple wet chemical method. The formation of 5-FU drug loaded composite was confirmed using Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore, the in vivo biodistribution and tumor targeting specificity of the 5-FU@FACS-Mn:ZnS in the tumor-bearing mice was conducted based on the Zn2+ tissue bioaccumulation using inductively coupled plasma (ICP) spectroscopy. In addition to the characterization, the in vitro release profile of 5-FU from the conjugates investigated under diffusion controlled method demonstrated a controlled release behaviour as compared against the release behaviour of free 5-FU drug. The as-synthesized 5-FU@FACS-Mn:ZnS nanoparticle (NP) systemically induced higher level of apoptosis in breast cancer cells in vitro as compared to cells treated with free 5-FU drug following both cell cycle and annexin assays, respectively. Also, the in vivo toxicity assessment of the 5-FU@FACS-Mn:ZnS NPs as compared to the control did not cause any significant increase in the activities of the liver and kidney function biomarkers, malondialdehyde (MDA) and nitric oxide (NO) levels. However, based on the FA-FRs chemistry, the 5-FU@FACS-Mn:ZnS NPs specifically accumulated in the tumor of the tumor-bearing mice and thus contributed to the smaller tumor size and less event of metastasis was observed in the lungs when compared to the tumor-bearing mice groups treated with the free 5-FU drug. In summary, the results demonstrated that the 5-FU@FACS-Mn:ZnS QDs exhibits selective anti-tumor effect in MDA-MB231 breast cancer cells in vitro and 4TI breast cancer cells in vivo, providing a blueprint for improving the 5-FU efficacy and tumor targeting specificity with limited systemic toxicity.
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spelling upm-565872017-08-03T04:54:35Z http://psasir.upm.edu.my/id/eprint/56587/ In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system Bwatanglang, Ibrahim Birma Faruq, Mohammad Yusof, Nor Azah Abdullah, Jaafar Mohammed Alitheen, Noorjahan Banu Hussein, Mohd Zubir Abu, Nadiah Mohamad, Nurul Elyani Nordin, Noraini Zamberi, Nur Rizi Yeap, Swee Keong In this study, we modulated the anti-cancer efficacy of 5-Fluorouracil (5-FU) using a carrier system with enhanced targeting efficacy towards folate receptors (FRs) expressing malignant tissues. The 5-FU drug was loaded onto Mn-ZnS quantum dots (QDs) encapsulated with chitosan (CS) biopolymer and conjugated with folic acid (FA) based on a simple wet chemical method. The formation of 5-FU drug loaded composite was confirmed using Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore, the in vivo biodistribution and tumor targeting specificity of the 5-FU@FACS-Mn:ZnS in the tumor-bearing mice was conducted based on the Zn2+ tissue bioaccumulation using inductively coupled plasma (ICP) spectroscopy. In addition to the characterization, the in vitro release profile of 5-FU from the conjugates investigated under diffusion controlled method demonstrated a controlled release behaviour as compared against the release behaviour of free 5-FU drug. The as-synthesized 5-FU@FACS-Mn:ZnS nanoparticle (NP) systemically induced higher level of apoptosis in breast cancer cells in vitro as compared to cells treated with free 5-FU drug following both cell cycle and annexin assays, respectively. Also, the in vivo toxicity assessment of the 5-FU@FACS-Mn:ZnS NPs as compared to the control did not cause any significant increase in the activities of the liver and kidney function biomarkers, malondialdehyde (MDA) and nitric oxide (NO) levels. However, based on the FA-FRs chemistry, the 5-FU@FACS-Mn:ZnS NPs specifically accumulated in the tumor of the tumor-bearing mice and thus contributed to the smaller tumor size and less event of metastasis was observed in the lungs when compared to the tumor-bearing mice groups treated with the free 5-FU drug. In summary, the results demonstrated that the 5-FU@FACS-Mn:ZnS QDs exhibits selective anti-tumor effect in MDA-MB231 breast cancer cells in vitro and 4TI breast cancer cells in vivo, providing a blueprint for improving the 5-FU efficacy and tumor targeting specificity with limited systemic toxicity. Elsevier 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/56587/1/In%20vivo%20tumor%20targeting%20and%20anti-tumor%20effects%20of%205-fluororacil%20loaded%2C%20folic%20acid%20targeted%20quantum%20dot%20system.pdf Bwatanglang, Ibrahim Birma and Faruq, Mohammad and Yusof, Nor Azah and Abdullah, Jaafar and Mohammed Alitheen, Noorjahan Banu and Hussein, Mohd Zubir and Abu, Nadiah and Mohamad, Nurul Elyani and Nordin, Noraini and Zamberi, Nur Rizi and Yeap, Swee Keong (2016) In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system. Journal of Colloid and Interface Science, 480. pp. 146-158. ISSN 0021-9797; ESSN: 1095-7103 http://www.sciencedirect.com/science/article/pii/S0021979716304611?via%3Dihub 10.1016/j.jcis.2016.07.011
spellingShingle Bwatanglang, Ibrahim Birma
Faruq, Mohammad
Yusof, Nor Azah
Abdullah, Jaafar
Mohammed Alitheen, Noorjahan Banu
Hussein, Mohd Zubir
Abu, Nadiah
Mohamad, Nurul Elyani
Nordin, Noraini
Zamberi, Nur Rizi
Yeap, Swee Keong
In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
title In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
title_full In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
title_fullStr In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
title_full_unstemmed In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
title_short In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
title_sort in vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system
url http://psasir.upm.edu.my/id/eprint/56587/
http://psasir.upm.edu.my/id/eprint/56587/
http://psasir.upm.edu.my/id/eprint/56587/
http://psasir.upm.edu.my/id/eprint/56587/1/In%20vivo%20tumor%20targeting%20and%20anti-tumor%20effects%20of%205-fluororacil%20loaded%2C%20folic%20acid%20targeted%20quantum%20dot%20system.pdf