Surface Coating Directed Cellular Delivery of TAT-Functionalized Quantum Dots

Abstract

TAT peptide functionalized shell-core ZnS-CdSe quantum dots (QDs) have been prepared by three different methods, direct ligand exchange with cysteine-terminated TAT (TAT-QD(lig exch)), and covalent conjugation to QDs coated with silanes (TAT-QD(silica)) and polyacrylate derivatives (TAT-QD(polyacrylate)). The silica and polyacrylate coatings incorporated multiple primary and secondary amines, introducing positive surface charges onto the QDs, providing high water solubility and sites for peptide conjugation, while inducing the "proton sponge effect". The different coating methods produced particles of different sizes, surface charges, and colloidal stability; these factors jointly influenced the cellular uptake and subcellular localization of these particles. As the particle size increased, (TAT-QD(lig exch) (6 nm) < TAT-QD(silica) (10 nm) < QD(polyacrylate) (25 nm)), both the particle surface charge and cellular uptake increased. The smaller TAT-QD(lig exch) and TAT-QD(silica) particles were localized mainly in the perinuclear regions, while the larger TAT-QD(polyacrylate) particles were localized in both the perinuclear regions and the lysosomes. Compared to the other TAT-QDs, TAT-QD(lig-exch) has a lower colloidal stability and was more cytotoxic due to the weak binding of the ligands.

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

“…It results in stable and chemically well defined conjugates, involving mainly disulfide or thioester linkages. For this type of conjugation, CPPs such as Tat, pANT, transportan, pVEC, and arginine-rich peptides were commonly used (Muratovska and Eccles, 2004;Hu et al, 2009;Wei et al, 2009;Sawant and Torchilin, 2011;Regberg et al, 2012). The advantages of the covalent bonding for in vivo applications are reproducibility of the procedure as well as control of the stoichiometry of as-prepared conjugates.…”

Interaction of folate-conjugated human serum albumin (HSA) nanoparticles with tumour cells

“…Among the components of the NPs, only N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) was expected to exhibit cytotoxicity, because cationic polymers may strongly interact with anionic cellular surfaces and therefore compromise the integrity of cellular membranes (Wei et al, 2009). HSA NPs prepared with EDC and folic acid had no influence on cell viability in HFF cells but decreased the viability of UKF-NB-3 cells (IC50 = 0.24 mg/ml) and 101/8 cells (IC50 = 0.54 mg/ml) at high concentrations, as indicated by MTT assay (Fig.…”

Cell-penetrating peptides for nanomedicine – how to choose the right peptide

“…Increasing their size and surface charge improved cellular uptake while diminishing their targeting specificity. Wei et al were also able to demonstrate that nanoparticles with a diameter exceeding 13 nm were primarily taken up by endosomal pathways [121]. Another efficient conjugation technique was employed by Lagerholm et al, who utilized biotinylated oligoarginine in order to equip commercially available streptavidin-coated QDs with cellpenetrating properties for multicolour staining of mammalian cells [embryonic mouse fibroblasts (Swiss 3T3), human endothelial cells (HeLa), and human osteoblastlike cells (MG63)].…”