Designing red-fluorescent superparamagnetic nanoparticles by conjugation with gold clusters.

Photoluminescent (PL) metal and metal oxide nanoclusters (NCs), with a size of just several nanometers, are a separate class of nanomaterials abundant with new attractive optical, physical, and chemical properties and biocompatibility. However, the synthesis of PL magnetic NCs via attachment of PL NCs to iron oxide-based nanoparticles (NPs) is still problematic. Motivated by this, herein, we report the development of a microwave-driven conjugation approach of red-fluorescent gold nanoclusters (BSA@AuNCs) to superparamagnetic NPs. Synthesized CoFe2O4@AuNCs possess strong photoluminescence in water and ethanol media as well as good colloidal and optical stability, and magnetization response. High-resolution transmission electron microscopy (HRTEM), steady-state and time-resolved photoluminescence spectroscopy, X-ray powder diffraction (XRD), and magnetic measurements from ambient to cryogenic temperatures were applied for structural characterization and evaluation of optical and magnetic properties of the synthesized species.

Biodistribution of Multimodal Gold Nanoclusters Designed for Photoluminescence-SPECT/CT Imaging and Diagnostic.

Highly biocompatible nanostructures for multimodality imaging are critical for clinical diagnostics improvements in the future. Combining optical imaging with other techniques may lead to important advances in diagnostics. The purpose of such a system would be to combine the individual advantages of each imaging method to provide reliable and accurate information at the site of the disease bypassing the limitations of each. The aim of the presented study was to evaluate biodistribution of the biocompatible technetium-99m labelled bovine serum albumin-gold nanoclusters (99mTc-BSA-Au NCs) as photoluminescence-SPECT/CT agent in experimental animals. It was verified spectroscopically that radiolabelling with 99mTc does not influence the optical properties of BSA-Au NCs within the synthesized 99mTc-BSA-Au NCs bioconjugates. Biodistribution imaging of the 99mTc-BSA-Au NCs in Wistar rats was performed using a clinical SPECT/CT system. In vivo imaging of Wistar rats demonstrated intense cardiac blood pool activity, as well as rapid blood clearance and accumulation in the kidneys, liver, and urinary bladder. Confocal images of kidney, liver and spleen tissues revealed no visible uptake indicating that the circulation lifetime of 99mTc-BSA-Au NCs in the bloodstream might be too short for accumulation in these tissues. The cellular uptake of 99mTc-BSA-Au NCs in kidney cells was also delayed and substantial accumulation was observed only after 24-h incubation. Based on our experiments, it was concluded that 99mTc-BSA-Au NCs could be used as a contrast agent and shows promise as potential diagnostic agents for bloodstream imaging of the excretory organs in vivo.

Hitchhiking Nanoparticles: Mesenchymal Stem Cell-Mediated Delivery of Theranostic Nanoparticles.

Nanotechnology has emerged as a promising solution to permanent elimination of cancer. However, nanoparticles themselves lack specificity to tumors. Due to enhanced migration to tumors, mesenchymal stem cells (MSCs) were suggested as cell-mediated delivery vehicles of nanoparticles. In this study, we have constructed a complex composed of photoluminescent quantum dots (QDs) and a photosensitizer chlorin e6 (Ce6) to obtain multifunctional nanoparticles, combining cancer diagnostic and therapeutic properties. QDs serve as energy donors-excited QDs transfer energy to the attached Ce6 via Förster resonance energy transfer, which in turn generates reactive oxygen species. Here, the physicochemical properties of the QD-Ce6 complex and singlet oxygen generation were measured, and the stability in protein-rich media was evaluated, showing that the complex remains the most stable in protein-free medium. In vitro studies on MSC and cancer cell response to the QD-Ce6 complex revealed the complex-loaded MSCs' potential to transport theranostic nanoparticles and induce cancer cell death. In vivo studies proved the therapeutic efficacy, as the survival of tumor-bearing mice was statistically significantly increased, while tumor progression and metastases were slowed down.

Uptake and distribution of carboxylated quantum dots in human mesenchymal stem cells: cell growing density matters.

BACKGROUND: Human mesenchymal stem cells (MSCs) have drawn much attention in the field of regenerative medicine for their immunomodulatory and anti-inflammatory effects. MSCs possess specific tumor-oriented migration and incorporation highlighting the potential for MSCs to be used as an ideal carrier for anticancer agents. Bone marrow is the main source of MSCs for clinical applications. MSCs tracking in vivo is a critical component of the safety and efficacy evaluation of therapeutic cell products; therefore, cells must be labeled with contrast agents to enable visualization of the MSCs migration in vivo. Due to their unique properties, quantum dots (QDs) are emerging as optimal tools in long-term MSC optical imaging applications. The aim of this study was to investigate the uptake dynamics, cytotoxity, subcellular and extracellular distribution of non-targeted carboxylated quantum dots in human bone marrow MSCs at different cell growing densities. RESULTS: QDs had no negative impact on MSC viability throughout the experiment and accumulated in all observed cells efficiently; however, in some MSCs QDs induced formation of lipid droplets. At low cell growing densities QDs distribute within MSCs cytoplasm already after 1 h of incubation reaching saturation after 6 h. After 24 h QDs localize mainly in the perinuclear region of the cells in endosomes. Interestingly, in more confluent culture QDs localize mostly outside MSCs. QDs abundantly mark MSC long filopodia-like structures attaching neighboring cells. At high cell density cultivation, we for the first time demonstrated that carboxylated QDs localize in human bone marrow MSC extracellular matrix. Moreover, we observed that average photoluminescence lifetime of QDs distributed in extracellular matrix are longer than lifetimes of QDs entrapped in endocytic vesicles; thus, for the first time showing the possibility to identify and distinguish localization of QDs in various extracellular and intracellular structures using fluorescence-lifetime imaging microscopy without additional staining assays. CONCLUSION: Carboxylated QDs can be used as nonspecific and effective dye for staining of human bone marrow MSCs and their specific extracellular structures. These results are promising in fundamental stem cell biology as well as in cellular therapy, anticancer drug delivery and tissue engineering.