Efficient Subcellular Targeting to the Cell Nucleus of Quantum Dots Densely Decorated with a Nuclear Localization Sequence Peptide

Organelle-targeted drug delivery can enhance the efficiency of the intracellularly acting drugs and reduce their toxicity. We generated core–shell type CdSe-ZnS quantum dots (QDs) densely decorated with NLS peptidic targeting residues using a 3-stage decoration approach and investigated their endocytosis and nuclear targeting efficiencies. The diameter of the generated QDs increased following the individual decoration stages (16.3, 18.9, and 21.9 nm), the ζ-potential became less negative (−33.2, −17.5, and −11.9 mV), and characteristic changes appeared in the FTIR spectra following decoration with the linker and NLS peptides. Quantitative analysis of the last decoration stage revealed that 37.9% and 33.2% of the alkyne-modified NLS groups that were added to the reaction mix became covalently attached or adsorbed to the QDs surface, respectively. These numbers correspond to 63.6 and 55.7 peptides conjugated or adsorbed to a single QD (the surface density of 42 and 37 conjugated and adsorbed peptides per 1000 nm² of the QDs surface), which is higher than in the majority of previous studies that reported decoration efficiencies of formulations intended for nuclear-targeted drug delivery. QDs decorated with NLS peptides undergo more efficient endocytosis, as compared to other investigated QDs formulations, and accumulated to a higher extent in the cell nucleus or in close vicinity to it (11.9%, 14.6%, and 56.1% of the QDs endocytosed by an average cell for the QD-COOH, QD-azide, and QD-NLS formulations, respectively). We conclude that dense decoration of QDs with NLS residues increased their endocytosis and led to their nuclear targeting (preferential accumulation in the cells nuclei or in close vicinity to them). The experimental system and research tools that were used in this study allow quantitative investigation of the mechanisms that govern the QDs nuclear targeting and their dependence on the formulation properties. These findings will contribute to the development of subcellularly targeted DDSs that will deliver specific drugs to the nuclei of the target cells and will enhance efficacy and reduce toxicity of these drugs

Fluorescence Energy Transfer from Doped to Undoped Quantum Dots

We report here the fluorescence energy transfer between two types of inorganic semiconductor nanocrystals: one is doped (d-dots) with optically active transition metal ion and other one is the undoped quantum dots (q-dots). While the two types of undoped quantum dots do not show significant energy transfer, the doped quantum dots under similar conditions show efficient energy transfer to the undoped one. The difference in the lifetime makes the doped quantum dots as donor for quantum dots. Exploring Cu-doped and Mn-doped d-dots as donor with the suitable size of CdSe q-dots as acceptor, we report here a detailed study of d-dot to q-dot energy transfer and investigate the possible mechanism

Acidic pH-Triggered Release of Doxorubicin from Ligand-Decorated Polymeric Micelles Potentiates Efficacy against Cancer Cells

Current chemotherapeutic strategies against various intractable cancers are futile due to inefficient delivery, poor bioavailability, and inadequate accumulation of anticancer drugs in the diseased site with toxicity caused to the healthy neighboring cells. Drug delivery systems aiming to deliver effective therapeutic concentrations to the site of action have emerged as a promising approach to address the above-mentioned issues. Thus, as several receptors have been identified as being overexpressed on cancer cells including folate receptor (FR), where up to 100–300 times higher overexpression is shown in cancer cells compared to healthy cells, approximately 1–10 million receptor copies per cancer cell can be targeted by a folic acid (FA) ligand. Herein, we developed FA-decorated and doxorubicin-conjugated polymeric micelles of 30 nm size. The hydrophilic block comprises poly(ethylene glycol) units, and the hydrophobic block contains aspartic acid. Decoration of FA on the micelle surface induces ligand–receptor interaction, resulting in enhanced internalization into the cancer cell and inside the endolysosomal compartment. Under acidic pH, the micelle structure is disrupted and the hydrazone bond is cleaved, which covalently binds the doxorubicin with the hydrophobic backbone of the polymer and release the drug. We observed that the cellular uptake and nuclear colocalization of the targeted micelle are 2–4 fold higher than the control micelle at various incubation times in FR-overexpressed various cancer cell lines (KB, HeLa, and C6). These results indicate significant prospects for anticancer therapy as an effective and translational treatment strategy