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5-Fluororaucil (5-FU) as anti-cancer drug was reported to induce thymidine synthase (TS) overexpression and cancer cell resistance. To improve its therapeutic efficacy and selective targeting, here we developed a targeted delivery system mediated by the active ligand-folate receptor chemistry to deliver the 5-FU drug selectively into the tumor microenvironment. The preparation was achieved by exploring chitosan (CS)-biopolymer based system with folic acid (FA)-conjugation. The 5-FU@FACS-Mn:ZnS quantum dots (QDs) based on the histological assessment conducted in the 4T1 challenged mice showed an improved tumor remission in the liver, spleen and lungs. The 5-FU@FACS-Mn:ZnS composite induced anti-proliferative properties in these organs as compared to the free 5-FU drug. Unlike the 5-FU@FACS-Mn:ZnS treated groups which showed some specific morphological changes such as cell shrinkage without obvious presence of adipocytes, the excised section of the tumor in the untreated control group and the free 5-FU drug treated group showed necrotic and degenerated cells; these cells are multifocally distributed in the tumor mass with evidence of widely distributed adipocytes within the tumor mass. These findings suggest that the 5-FU@FACS-Mn:ZnS composite has a superior role during the induction of apoptosis in the 4T1 cells as compared to the free 5-FU drug treated groups. The results of the study therefore suggest that the impregnation of 5-FU anti-cancer drug within the FACS-Mn:ZnS system significantly improves its selective targeting efficacy, in addition to improving the anti-proliferative properties and attenuate possible tumor resistances to the 5-FU drug.

or the past few decades, many acquisitions were developed to unraveled cancer chemistry by designing smarter nanomaterials that can selectively target cancer cells, respond to its microenvironment and possibly support non-invasive diagnosis. However, despites the encouraging achievements in line with this concept in vitro, the use of these theranostics nanomaterials in vivo remain an unfinished business. Based on this account, a nanocomposite for targeted delivery and imaging application was developed. The rational was implemented by exploring chitosan-biopolymer based system mediated by folic acid-conjugation with affinity towards folate receptors expressed by cancer cells. The folic acid conjugated chitosan-based system was further equipped with a fluorescence imaging contrast agent (Mn:ZnS) to deliver 5-Fluororaucil anti-cancer drugs selectively into tumor-microenvironment. On the basis of these strategies, four sequential wet chemistry methods was adopted to prepare the 5-FU@FACS-Mn:ZnS nanocomposite. The as-prepared nanocomposite shows an average particle size distribution of 8.42 ± 1.79 nm and emit orange-red fluorescence at ~600nm. The strategy for the preparation involves physicochemical optimization of the nanocomposites for controlled drug release, tumor targeting specificity and bioavailability. The result was accomplished by testing and optimizing the physical properties of the materials using Fourier transform infrared, ultraviolet-visible spectroscopy, thermogravimetric analysis/differential scanning calorimetry, transmission electron microscopy, field emission scanning electron microscopy/energy dispersive X-ray, X-ray diffraction, X-ray fluorescence, X-ray photoelectron spectroscopy, fluorescence microscopy and dynamic light scattering instrumentations. The in vitro result showed that the as-synthesized 5-FU@FACS-Mn:ZnS nanocomposite when compared to the pure 5-FU anti-cancer drugs induced high level of apoptosis, selectivity and allowed fluorescence

Ibrahim Birma Bwatanglang,1,2 Faruq Mohammad,3 Nor Azah Yusof,1,3 Jaafar Abdullah,1 Mohd Zobir Hussein,3 Noorjahan Banu Alitheen,4 Nadiah Abu4 1Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Department of Chemistry, Faculty of Science, Adamawa State University, Mubi, Nigeria; 3Institute of Advanced Technology, 4Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit

In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hyp