Novel POSS-PCU Nanocomposite Material as a Biocompatible Coating for Quantum Dots.

Quantum dots (QDs) are fluorescent nanoparticles with unique photophysical properties that enable them to potentially replace traditional organic dyes and fluorescent proteins in various bioimaging applications. However, the inherent toxicity of their cores based on cadmium salts limits their widespread biomedical use. We have developed a novel nanocomposite polymer emulsion based on polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) that can be used to coat quantum dots to nullify their toxicity and enhance photostability. Here we report the synthesis and characterization of a novel POSS-PCU nanocomposite polymer emulsion and describe its application for coating QDs for biological application. The polymer was synthesized by a process of emulsion polymerization and formed stable micelles of ∼33 nm in diameter. CdTe/CdS/ZnS QDs were efficiently stabilized by the polymer emulsion through encapsulation within the polymer micelles. Characterization studies showed no significant change in the unique photophysical properties of QDs after coating. The polymer was biocompatible to HepG2, HUVECs, and mouse skeletal muscle cells at 2.5% after 24 h exposure on in vitro testing. Polymer encapsulated QDs showed enhanced photostability on exposure to high degrees of UV irradiation and air as well as significantly reduced cytotoxicity on exposure to HepG2 cells at 30 µg/mL for 24 h. We have therefore concluded that the POSS-PCU polymer emulsion has the potential to make a biocompatible and photostable coating for QDs enabling a host of biomedical applications to take this technology to the next level.

Near-infrared quantum dots for HER2 localization and imaging of cancer cells.

BACKGROUND: Quantum dots are fluorescent nanoparticles with unique photophysical properties that allow them to be used as diagnostic, therapeutic, and theranostic agents, particularly in medical and surgical oncology. Near-infrared-emitting quantum dots can be visualized in deep tissues because the biological window is transparent to these wavelengths. Their small sizes and free surface reactive groups that can be conjugated to biomolecules make them ideal probes for in vivo cancer localization, targeted chemotherapy, and image-guided cancer surgery. The human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 25%-30% of breast cancers. The current methods of detection for HER2 status, including immunohistochemistry and fluorescence in situ hybridization, are used ex vivo and cannot be used in vivo. In this paper, we demonstrate the application of near-infrared-emitting quantum dots for HER2 localization in fixed and live cancer cells as a first step prior to their in vivo application. METHODS: Near-infrared-emitting quantum dots were characterized and their in vitro toxicity was established using three cancer cell lines, ie, HepG2, SK-BR-3 (HER2-overexpressing), and MCF7 (HER2-underexpressing). Mouse antihuman anti-HER2 monoclonal antibody was conjugated to the near-infrared-emitting quantum dots. RESULTS: In vitro toxicity studies showed biocompatibility of SK-BR-3 and MCF7 cell lines with near-infrared-emitting quantum dots at a concentration of 60 µg/mL after one hour and 24 hours of exposure. Near-infrared-emitting quantum dot antiHER2-antibody bioconjugates successfully localized HER2 receptors on SK-BR-3 cells. CONCLUSION: Near-infrared-emitting quantum dot bioconjugates can be used for rapid localization of HER2 receptors and can potentially be used for targeted therapy as well as image-guided surgery.

Altered sensitivity to nitric oxide donors, induced by intravascular infusion of quantum dots, in murine mesenteric arteries.

Quantum dots (QDs) are utilised in imaging diagnostics, tissue engineering and medical therapeutics, however, their influence on vascular function is not ascertained. Here, we examined small mesenteric arterial responses after acute intravascular exposure to QDs. Incubation in mercaptoundecanoic acid (MUA)-coated QDs (at 15 µg/mL) had no influence on endothelial-dependent dilator responses (Acetylcholine; Ach) but led to an attenuated relaxation to the nitric oxide donor, sodium nitroprusside (SNP). Conversely, incubation in POSS-PCU coated QDs (at 15 µg/mL) led to attenuated Ach responses (10(-11)-10(-3)M; n=5, P<0.05), but had no influence on SNP-induced relaxation. At lower concentrations of POSS-PCU coated QDs (5 µg/mL), Ach responses were preserved. We demonstrate that acute exposure to QDs, can attenuate vasodilation but not vasoconstriction, and is dependent on their surface coatings. Our findings have implications in QD use for imaging diagnostics in disease states, where SNP based drugs are used in therapeutic intervention. FROM THE CLINICAL EDITOR: In this paper, the influence of quantum dots on vascular function is investigated---an important aspect to consider with the growing utility of quantum dots in imaging diagnostics, tissue engineering and medical therapeutics.

A novel POSS-coated quantum dot for biological application.

Quantum dots (QDs) are fluorescent semiconductor nanocrystals that have the potential for major advancements in the field of nanomedicine through their unique photophysical properties. They can potentially be used as fluorescent probes for various biomedical imaging applications, including cancer localization, detection of micrometastasis, image guided surgery, and targeted drug delivery. Their main limitation is toxicity, which requires a biologically compatible surface coating to shield the toxic core from the surrounding environment. However, this leads to an increase in QD size that may lead to problems of excretion and systemic sequestration. We describe a one pot synthesis, characterization, and in vitro cytotoxicity of a novel polyhedral oligomeric silsesquioxane (POSS)-coated CdTe-cored QD using mercaptosuccinic acid (MSA) and D-cysteine as stabilizing agents. Characterization was performed using transmission electron microscopy Fourier transform infrared spectroscopy, and photoluminescence studies. POSS-coated QDs demonstrated high colloidal stability and enhanced photostability on high degrees of ultraviolet (UV) excitation compared to QDs coated with MSA and D-cysteine alone (P value < 0.05). In vitro toxicity studies showed that both POSS and MSA-QDs were significantly less toxic than ionized salts of Cd(+2) and Te(-2). Confocal microscopy confirmed high brightness of POSS-QDs in cells at both 1 and 24 hours, indicating that these QDs are rapidly taken up by cells and remain photostable in a biological environment. We therefore conclude that a POSS coating confers biological compatibility, photostability, and colloidal stability while retaining the small size and unique photophysical properties of the QDs. The amphiphilic nature of the coating allows solubility in aqueous solutions and rapid transfer across cell membranes, enabling the use of lower concentrations of the QDs for an overall reduced toxicity particularly for prolonged live cell and in vivo imaging applications.

Semiconductor quantum dots as fluorescent probes for in vitro and in vivo bio-molecular and cellular imaging.

Over the years, biological imaging has seen many advances, allowing scientists to unfold many of the mysteries surrounding biological processes. The ideal imaging resolution would be in nanometres, as most biological processes occur at this scale. Nanotechnology has made this possible with functionalised nanoparticles that can bind to specific targets and trace processes at the cellular and molecular level. Quantum dots (QDs) or semiconductor nanocrystals are luminescent particles that have the potential to be the next generation fluorophores. This paper is an overview of the basics of QDs and their role as fluorescent probes for various biological imaging applications. Their potential clinical applications and the limitations that need to be overcome have also been discussed.