Dual-functional supramolecular nanohybrids of quantum dot/biopolymer/chemotherapeutic drug for bioimaging and killing brain cancer cells in vitro

Abstract

Glioblastoma (GBM) is the utmost aggressive and lethal primary brain cancer, which has a poor prognosis and remains virtually incurable. Nanomedicine with emerging disruptive nanotechnology alternatives, including designed supramolecular nanohybrids has excellent potential as multimodal tools against cancer by combining nanomaterials, biomacromolecules, and drugs. Thus, we developed and constructed for the first time quantum dot-biopolymer-drug nanohybrids based on host-guest chemistry for simultaneous bioimaging, targeting, and anti-cancer drug delivery against GBM cells in vitro. ZnS fluorescent quantum dots (ZnS-QDs) were produced using chemically modified polysaccharide, carboxymethylcellulose (CMC), as water-soluble capping ligand and biofunctional layer via a facile one-step eco-friendly aqueous colloidal process at room temperature and physiological pH. These hybrid inorganic-organic nanocolloids (ZnS@CMC) were electrostatically conjugated with doxorubicin (DOX) anti-cancer drug forming innovative supramolecular complexes (ZnS@CMC-DOX) for amalgamating bioimaging and killing cancer cells. These nanoconjugates were characterized regarding their optical and physicochemical properties combined with morphological and structural features. The cytocompatibility was evaluated by MTT assay using healthy and GBM cells. The results showed that ultra-small ZnS-QDs were expertly produced uniform nanocolloids (average size = 3.6 nm). They demonstrated photoluminescence emission within the visible range of spectra. The cell viability results in vitro showed no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. In summary, the novelty of this research relies on using a nanotheranostic strategy for developing ZnS@CMC-DOX nanohybrids with supramolecular vesicle-like structures. They behaved simultaneously as active fluorescent nanoprobes and nanocarriers with modulated drug release for bioimaging and killing malignant glioma cells proving the high potential for applications in cancer nanomedicine.

Keywords: Cancer nanotheranostic; Fluorescent nanoparticles; Nanocarriers; Nanocolloids; Nanoconjugates; Nanohybrids; Nanomedicine; Nanoparticles.