P625Semiconductor quantum dots for innovative approaches in photodynamic diagnosis and therapy

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Abstract

In the past decade photodynamic diagnosis (PDD) and photodynamic therapy (PDT) have emerged as minimally invasive regimens for the detection and treatment of several cancers and precancerous lesions. Novel functional nanodrugs consisting of a semiconductor quantum dot (QD) linked to photoactive photosensitizers (PS) may offer promising possibilities for future non-invasive PDD and targeted PDT. Although intact QDs are biocompatible, they can undergo enzymatic degradation in living organisms, resulting in unwanted toxic effects of QDs or QD-PS conjugates (dark toxicity). Thus, conflicting evidence exists regarding the safety of QDs in pharmacy and medicine.

By systematic photophysical evaluation and in vitro as well as in vivo investigations we here determined possible dark toxicity of newly synthesized photoactive and water-soluble semiconductor QDs covered with 3-mercaptopropionic acid (MPA), a zinc sulfide (ZnS) shell or with thioglycolic acid (TGA) for protection against enzymatic degradation.

Atomic force and transmission electron microscopy, x-ray diffraction, thermal gravimetric method as well as IR-Raman, UV/Vis absorption, and steady-state and time-resolved fluorescence spectroscopies were used for QD characterization. QD accumulation and intracellular distribution was studied using fluorescence and confocal laser-scanning microscopy of urological and neuroendocrine gastrointestinal tumor cell models (Tera-1 and BON cells). Cell viability and effects on cell growth were assessed by impedance-based real-time proliferation assays (xCELLigence). In vivo evaluations were performed by use of the chorioallantoic membrane (CAM) assay method focusing on effects of QD on microvessel formation and morphology.

All QDs showed high water solubility and the size of the differently covered QDs was in the range of 2.5 – 4 nm. In vitro tests have brought into light that TGA-covered QDs did not exhibit any dark toxicity even at concentrations as high as 1 µmol/L, whereas incubation with ZnS-shell or MPA covered QDs resulted in dose-dependent dark toxic effects at concentrations in the nanomolar range. Toxic concentrations of the QDs were shown to inhibit the formation and changed the morphology of microvessel networks of developing CAMs.

The obtained results demonstrate that the functional coating of QDs with TGA maintains the good solubility in aqueous media and almost abolishes dark toxic effects, making them promising candidates for further coupling with photoactive PS, which in turn will lead to new diagnostic and therapeutic options in the treatment of many diseases.

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