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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 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 hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. Keywords: Mn:ZnS, quantum dots, theranostics, folic acid, cancer diagnosis, fluorescence imaging

Recent increase in the integration of nanotechnology and nanosciences to the biomedical sector fetches the human wellness through the development of sustainable treatment methodologies for cancerous tumors at all stages of their initiation and progression. This involves the development of multifunctional theranostic probes that effectively support for the early cancer diagnosis, avoiding non-target cell toxicity, controlled and customized anticancer drug release etc. Therefore, to advance the field of nanotechnology-based sustainable cancer treatment, we fabricated and tested the efficacy of anticancer drug-loaded magnetic hybrid nanoparticles (NPs) towards in vitro cell culture systems. The developed conjugate of NPs was incorporated with the functions of both controlled drug delivery and heat-releasing ability using Mn 3 O 4 (manganese oxide) magnetic core with Cu shell encapsulated within trimethyl chitosan (TMC) biopolymer. On characterization, the Cu@Mn 3 O 4 -TMC NPs were confirmed to have an approximate size of 130 nm with full agglomeration (as observed by the HRTEM) and crystal size of 92.95 ± 18.38 nm with tetragonal hausmannite phase for Mn 3 O 4 spinel structure (XRD). Also, the UV-Vis and FTIR analysis provided the qualitative and quantitative effects of 5-fluororacil (5-Fu) anticancer drug loading (max 68 %) onto the Cu@Mn 3 O 4 -TMC NPs. The DLS analysis indicated for the occurrence of no significant changes to the particle size (around 100 nm) of Cu@Mn 3 O 4 -TMC due to the solution dispersion thereby confirming for the aqueous stability of developed NPs. In addition, the magnetization values of Cu@Mn 3 O 4 -TMC NPs were measured to be 34 emu/g and a blocking temperature of 42 K. Further tests of magnetic hyperthermia by the Cu@Mn 3 O 4 -TMC/5-Fu NPs provided that the heat-releasing capacity (% ΔT at 15 min) increases with that of increased frequency, i.e. 28 % (440 Hz) > 22.6 % (240 Hz) > 18 % (44 Hz), and the highest specific power loss (SPL) value observed to be 488 W/g for water. Moreover, the 5-Fu drug release studies indicate that the release is high at a pH of 5.2 and almost all the loaded drug is getting delivered under the influence of the external magnetic field (430 Hz) due to the influence of both Brownian-rotation and Néel relaxation heat-mediated mechanism. The pharmacokinetic drug release studies have suggested for the occurrence of more than one model, i.e. First-order, Higuchi (diffusion), and Korsemeyer-Peppas (non-Fickian), in addition to hyperthermia. Finally, the in vitro cell culture systems (MCF-7 cancer and MCF-10 non-cancer) helped to differentiate the physiological changes due to the effects of hyperthermia and 5-Fu drug individually and as a combination of both. The observed differences of cell viability losses among both cell types are measured and discussed with the expression of heat shock proteins (HSPs) by the MCF-10 cells as against the MCF-7 cancer cells. We believe that the results generated in this project can be helpful for the designing of new cancer therapeutic models with nominal adverse effects on healthy normal cells and thus paving a way for the treatment of cancer and other deadly diseases in a sustainable manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, we tested the biosorption capacity of trimethyl chitosan (TMC)-ZnO nanocomposite (NC) for the adsorptive removal of Escherichia coli ( E. coli ) in aqueous suspension. For the formation of ZnO NPs, we followed the green synthesis route involving Terminalia mantaly (TM) aqueous leaf extract as a reducing agent, and the formed ZnO particles were surface-coated with TMC biopolymer. On testing of the physicochemical characteristics, the TM@ZnO/TMC (NC) hydrogel showed a random spherical morphology with an average size of 31.8 ± 2.6 nm and a crystal size of 28.0 ± 7.7 nm. The zeta potential of the composite was measured to be 23.5 mV with a BET surface area of 3.01 m 2 g -1 . The spectral profiles of TM@ZnO/TMC NC hydrogel on interaction with Escherichia coli ( E. coli ) revealed some conformational changes to the functional groups assigned to the stretching vibrations of N-H, C-O-C, C-O ring, and C=O bonds. The adsorption kinetics of TM@ZnO/TMC NC hydrogel revealed the pseudo-second-order as the best fit mechanism for the E. coli biosorption. The surface homogeneity and monolayer adsorption of the TM@ZnO/TMC NC hydrogel reflects majorly the entire adsorption mechanism, observed to display the highest correlation for Jovanovic, Redlich-Peterson, and Langmuir's isotherm models. Further, with the use of TM@ZnO/TMC NC hydrogel, we measured the highest adsorption capacity of E. coli to be 4.90 × 10 mg g -1 , where an in-depth mechanistic pathway was proposed by making use of the FTIR analysis.

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 Zn(2+) 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)