One-Pot Aqueous Synthesis of Fluorescent Ag-In-Zn-S Quantum Dot/Polymer Bioconjugates for Multiplex Optical Bioimaging of Glioblastoma Cells

Abstract

Cancer research has experienced astonishing advances recently, but cancer remains a major threat because it is one of the leading causes of death worldwide. Glioblastoma (GBM) is the most malignant brain tumor, where the early diagnosis is vital for longer survival. Thus, this study reports the synthesis of novel water-dispersible ternary AgInS2 (AIS) and quaternary AgInS2-ZnS (ZAIS) fluorescent quantum dots using carboxymethylcellulose (CMC) as ligand for multiplexed bioimaging of malignant glioma cells (U-87 MG). Firstly, AgInS2 core was prepared using a one-pot aqueous synthesis stabilized by CMC at room temperature and physiological pH. Then, an outer layer of ZnS was grown and thermally annealed to improve their optical properties and split the emission range, leading to core-shell alloyed nanostructures. Their physicochemical and optical properties were characterized, demonstrating that luminescent monodispersed AIS and ZAIS QDs were produced with average sizes of 2.2 nm and 4.3 nm, respectively. Moreover, the results evidenced that they were cytocompatible using in vitro cell viability assays towards human embryonic kidney cell line (HEK 293T) and U-87 MG cells. These AIS and ZAIS successfully behaved as fluorescent nanoprobes (red and green, resp.) allowing multiplexed bioimaging and biolabeling of costained glioma cells using confocal microscopy.

Fluorescent ZnS Quantum Dots–Phosphoethanolamine Nanoconjugates for Bioimaging Live Cells in Cancer Research

“…Nevertheless, it widely known that the QY can be significantly improved by postsynthesis thermal annealing at a higher temperature and by growing a semiconductor shell for passivating the surface defects. 26,34 Typical TEM image (Figure 1C) indicated the formation of uniformly dispersed spherical nanoparticles with estimated sizes of d = 3.3 ± 0.6 nm (Figure 1E), very coherent with the dimensions of ZnS QDs estimated by UV−vis measurements (i.e., 2r = 3.2 nm). Additionally, HRTEM images associated with SAED diffraction patterns (Figure 1D) confirmed the formation of crystalline semiconductor nanoparticles wellmatched with ZnS cubic structure (i.e., lattice (111), d = 0.31 ± 0.01 nm).…”

“…Nevertheless, it widely known that the QY can be significantly improved by postsynthesis thermal annealing at a higher temperature and by growing a semiconductor shell for passivating the surface defects. 26 , 34 …”

“…Different from processes using high temperatures and organometallic media, the aqueous colloidal synthesis of QDs frequently leads to higher density of surface defects that act as “trap states” in the recombination process of charges. Nevertheless, it widely known that the QY can be significantly improved by postsynthesis thermal annealing at a higher temperature and by growing a semiconductor shell for passivating the surface defects. , …”

Design and Development of Polysaccharide-Doxorubicin-Peptide Bioconjugates for Dual Synergistic Effects of Integrin-Targeted and Cell-Penetrating Peptides for Cancer Chemotherapy

“…The biopolymer was selected with lower degree of substitution (DS = 0.7) to favor biodegradability and, with a molecular mass ( M w = 250 000 Da), above the renal threshold, to prevent polymer–drug conjugates from rapid blood clearance and elimination from the body considering perspective clinical applications of these designed systems. In addition, according to the literature, the relative high-molecular-molar therapeutics may preferentially accumulate in tumors increasing the therapeutic action in vivo due to the enhanced permeation and retention (EPR) effects. ,− Moreover, based on previous studies in our group, using fluorescent quantum dots directly stabilized with CMC in aqueous media, , this cellulose derivative macromolecule can be internalized in tumoral and nontumoral cells without the presence of transmembrane vectors.…”

“…In addition, according to the literature, the relative highmolecular-molar therapeutics may preferentially accumulate in tumors increasing the therapeutic action in vivo due to the enhanced permeation and retention (EPR) effects. 16,32−35 Moreover, based on previous studies in our group, using fluorescent quantum dots directly stabilized with CMC in aqueous media, 36,37 this cellulose derivative macromolecule can be internalized in tumoral and nontumoral cells without the presence of transmembrane vectors.…”