Quantum dots (QDs) are attractive photoluminescence probes for biomedical imaging due to their unique photophysical properties. However, the potential toxicity of QDs has remained a major obstacle to their clinical use because they commonly incorporate the toxic heavy metal cadmium within the core of the QDs. In this work, we have evaluated a novel type of heavy metal-free/cadmium-free and biocompatible QD nanoparticles (bio CFQD® nanoparticles) with a good photoluminescence quantum yield. Sentinel lymph node mapping is an increasingly important treatment option in the management of breast cancer. We have demonstrated their potential for lymph node mapping by ex vivo imaging of regional lymph nodes after subcutaneous injection in the paw of rats. Using photoluminescence imaging and chemical extraction measurements based on elemental analysis by inductively coupled plasma mass spectroscopy, the quantum dots are shown to accumulate quickly and selectively in the axillary and thoracic regional lymph nodes. In addition, lifetime imaging microscopy of the QD photoluminescence indicates minimal perturbation to their photoluminescence properties in biological systems.
Quantum dot (QD) nanoparticles are highly promising contrast agents and probes for biomedical applications owing to their excellent photophysical properties. However, toxicity concerns about commonly used cadmium-based QDs hinder their translation to clinical applications. In this study we describe the in vivo biodistribution and toxicology of indium-based water soluble QDs in rats following intravenous administration. The biodistribution measured at up to 90 days showed that QDs mainly accumulated in the liver and spleen, with similar elimination kinetics to subcutaneous administration. Evidence for QD degradation in the liver was found by comparing photoluminescence measurements versus elemental analysis. No organ damage or histopathological lesions were observed for the QDs treated rats after 24 h, 1 and 4 weeks following intravenous administration at 12.5 mg/kg or 50 mg/kg. Analysis of serum biochemistry and complete blood counts found no toxicity. This work supports the strong potential of indium-based QDs for translation into the clinic.
The rising incidence
of antibiotic-resistant infections from contaminated surfaces in hospitals
or implanted medical devices has led to increasing interest in new
antibacterial surfaces. Photoactivatable surfaces that can generate
cytotoxic reactive oxygen species under exposure to ambient light
is a promising approach to inactivation of surface-borne microorganisms.
There is growing interest in the use of quantum dots (QDs) as light-harvesting
agents for photobactericidal applications, but the cadmium in commonly
used QDs will restrict clinical application. Herein, the photobactericidal
activity of novel polyurethane substrates containing cadmium-free
QDs was tested against clinical multidrug-resistant Gram-positive
and Gram-negative bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA) and a carbapenemase-producing
strain of Escherichia coli (E. coli). To enhance the capacity for reactive oxygen
species generation, QDs were incorporated into the polymer with a
photosensitizing dye, crystal violet. Close proximity between the
QD and dye enables electron and energy transfer processes leading
to generation of cytotoxic singlet oxygen and superoxide radicals.
A QD solution in cyclohexane was premixed with a solution of CV in
the more polar solvent, dichloromethane, to promote the formation
of QD–CV nanocomposite complexes via CV adsorption. This solution
was then used to embed the QDs and crystal violet into medical grade
polyurethane via swell–encapsulation. The combination of QD
and CV elicited significant synergistic antibacterial activity under
visible light against MRSA within 1 h (99.98% reduction) and E. coli within 4 h (99.96% reduction). Photoluminescence
lifetime and singlet oxygen phosphorescence measurements demonstrated
that interaction between the QDs and the crystal violet occurs within
the polymer and leads to enhanced generation of reactive oxygen species.
Strong inhibition of kill was observed using the superoxide scavenger,
superoxide dismutase. The efficacy of these QD–CV polymer substrates,
that can harvest light across the visible spectrum, against multidrug-resistant
bacteria demonstrates the feasibility of this approach.
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