Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

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 Mn 2+ 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.

Biodegradable poly(D,L-lactide-co-glycolide)/poly(L-γ-glutamic acid) nanoparticles conjugated to folic acid for targeted delivery of doxorubicin

“…FT-IR and UV-Vis analysis confirmed the conjugation of folic acid to PLGA/γ-PGA nanoparticles. The UV-Vis spectrum showed the distinctive band of folic acid assigned to the π-π* transition of the pteridine ring around 280 nm, which has been extensively described [41][42][43]. In the same way, the FT-IR spectrum of PLGA/γ-PGA-FA nanoparticles showed the characteristic peaks corresponding to the structural units of the folic acid molecule.…”

Folic Acid-Targeted Etoposide Cubosomes for Theranostic Application of Cancer Cell Imaging and Therapy

“…The anti-proliferative activity of ETP in different formulations was evaluated by the MTT assay using the human breast carcinoma cell line MCF-7, which expresses high levels of folate receptors [ 34 , 38 ]. In Figure 7B , ETP-Cubs demonstrated a significantly superior cytotoxicity compared with free drug.…”

Evaluation of cell penetrating peptide coated Mn:ZnS nanoparticles for paclitaxel delivery to cancer cells

“…Another study by Deng et al ., 2011 reported a high-quality Mn:ZnS NPs with tunable dual-color and multiphoton emissions and could be useful for bioimaging. This study also lacks the stability of Mn:ZnS NPs 11 This might be a possible reason for their limited use as drug delivery carrier except few reports such as folic acid targeted Mn:ZnS quantum dots for theranosis by Bwatanglang et al ., 2016 which has no serum stability of Mn:ZnS NPs reported 9 . Zhao et al ., 2017 reported that surface modification of Mn:ZnS NPs could improve the drug loading ability and optical properties 12 .…”

“…For example hemolytic chitosan was used to stabilize Mn:ZnS NPs by Bwatanglang., et al . 9 and mercaptopropionic acid was used to synthesize Mn:ZnS NPs by Zhao et al , 2015 10 .…”