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

Ibrahim Birma Bwatanglang, Faruq Mohammad, Nor Azah Yusof, Jaafar Abdullah, Noorjahan Banu Alitheen, Mohd Zubir Hussein, Nadiah Abu, Nurul Elyani Mohammed, Noraini Nordin, Nur Rizi Zamberi, Swee Keong Yeap

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)146-158
Number of pages13
JournalJournal of Colloid and Interface Science
Volume480
DOIs
Publication statusPublished - 15 Oct 2016
Externally publishedYes

Fingerprint

Folic Acid
Fluorouracil
Semiconductor quantum dots
Tumors
Bearings (structural)
Acids
Cells
Toxicity
Pharmaceutical Preparations
Tissue
Blueprints
Bioaccumulation
Malondialdehyde
Biopolymers
Nitric oxide
Inductively coupled plasma
Biomarkers
Cell death
Chitosan
Liver

Keywords

  • 5-Fluorouracil delivery
  • Anti-tumor
  • Folic acid
  • Mn:ZnS quantum dots
  • Targeted delivery
  • Theranostics

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Surfaces, Coatings and Films
  • Colloid and Surface Chemistry

Cite this

Bwatanglang, I. B., Mohammad, F., Yusof, N. A., Abdullah, J., Alitheen, N. B., Hussein, M. Z., ... Yeap, S. K. (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, 146-158. https://doi.org/10.1016/j.jcis.2016.07.011

In vivo tumor targeting and anti-tumor effects of 5-fluororacil loaded, folic acid targeted quantum dot system. / Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Alitheen, Noorjahan Banu; Hussein, Mohd Zubir; Abu, Nadiah; Mohammed, Nurul Elyani; Nordin, Noraini; Zamberi, Nur Rizi; Yeap, Swee Keong.

In: Journal of Colloid and Interface Science, Vol. 480, 15.10.2016, p. 146-158.

Research output: Contribution to journalArticle

Bwatanglang, IB, Mohammad, F, Yusof, NA, Abdullah, J, Alitheen, NB, Hussein, MZ, Abu, N, Mohammed, NE, Nordin, N, Zamberi, NR & Yeap, SK 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, vol. 480, pp. 146-158. https://doi.org/10.1016/j.jcis.2016.07.011
Bwatanglang, Ibrahim Birma ; Mohammad, Faruq ; Yusof, Nor Azah ; Abdullah, Jaafar ; Alitheen, Noorjahan Banu ; Hussein, Mohd Zubir ; Abu, Nadiah ; Mohammed, 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. In: Journal of Colloid and Interface Science. 2016 ; Vol. 480. pp. 146-158.
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