Three-dimensional (3D) rapid prototyping technology based on near-infrared light-induced polymerization of photocurable compositions containing upconversion nanomaterials has been explored. For this aim, the rationally-designed core/shell upconversion nanoparticles NaYF4:Yb3+,Tm3+/NaYF4, with the distinct ultraviolet-emitting lines and unprecedentedly high near-infrared to ultraviolet conversion efficiency of have been used. The upconverted ultraviolet photons were capable to efficiently activate photoinitiators contained in light-sensitive resins under moderate intensities of NIR excitation below 10 W cm−2 and induce generation of radicals and photopolymerization in situ. Near infrared-activated polymerization process, both at the millimeter and sub-micron scales, was investigated. Polymeric macro- and microstructures were fabricated by means of near infrared laser scanning photolithography in the volume of liquid photocurable compositions with focused laser light at 975 nm wavelength. Examination of the polymerization process in the vicinity of the nanoparticles shows strong differences in the rate of polymer shell growth on flat and edge nanoparticle sides. This phenomenon mainly defines the resolution of the demonstrated near infrared - ultraviolet 3D printing technology at the micrometer scale level.

Melanoma is one of the most aggressive and lethal form of cancer. Photodynamic therapy (PDT) is a clinically approved technique for cancer treatment, including non-melanoma skin cancer. However, the most of conventional photosensitizers are of low efficacy against melanoma due to the possible dark toxicity at high drug concentrations, melanin pigmentation, and induction of anti-oxidant defense mechanisms. In the current research we propose non-toxic flavin mononucleotide (FMN), which is a water-soluble form of riboflavin (vitamin B2) as a promising agent for photodynamic therapy of melanoma. We demonstrated selective accumulation of FMN in melanoma cells in vivo and in vitro in comparison with keratinocytes and fibroblasts. Blue light irradiation with dose 5 J/cm 2 of melanoma cells pre-incubated with FMN led to cell death through apoptosis. Thus, the IC 50 values of human melanoma A375, Mel IL, and Mel Z cells were in a range of FMN concentration 10–30 µM that can be achieved in tumor tissue under systemic administration. The efficiency of reactive oxygen species (ROS) generation under FMN blue light irradiation was measured in single melanoma cells by a label-free technique using an electrochemical nanoprobe in a real-time control manner. Melanoma xenograft regression in mice was observed as a result of intravenous injection of FMN followed by blue-light irradiation of tumor site. The inhibition of tumor growth was 85–90% within 50 days after PDT treatment.

Riboflavin (Rf) is a vitamin and endogenous photosensitizer capable to generate reactive oxygen species (ROS) under UV-blue irradiation and kill cancer cells, which are characterized by the enhanced uptake of Rf. We confirmed its phototoxicity on human breast adenocarcinoma cells SK-BR-3 preincubated with 30-μM Rf and irradiated with ultraviolet light, and proved that such Rf concentrations (60 μM) are attainable in vivo in tumour site by systemic intravascular injection. In order to extend the Rf photosensitization depth in cancer tissue to 6 mm in depth, we purpose-designed core/shell upconversion nanoparticles (UCNPs, NaYF4:Yb3+:Tm3+/NaYF4) capable to convert 2% of the deeply-penetrating excitation at 975 nm to ultraviolet-blue power. This power was expended to photosensitise Rf and kill SK-BR-3 cells preincubated with UCNPs and Rf, where the UCNP-Rf energy transfer was photon-mediated with ~14% Förster process contribution. SK-BR-3 xenograft regression in mice was observed for 50 days, following the Rf-UCNPs peritumoural injection and near-infrared light photodynamic treatment of the lesions.

Abstract. Innovative luminescent nanomaterials, termed upconversion nanoparticles (UCNPs), have demonstrated considerable promise as molecular probes for high-contrast optical imaging in cells and small animals. The feasibility study of optical diagnostics in humans is reported here based on experimental and theoretical modeling of optical imaging of an UCNP-labeled breast cancer lesion. UCNPs synthesized in-house were surface-capped with an amphiphilic polymer to achieve good colloidal stability in aqueous buffer solutions. The scFv4D5 mini-antibodies were grafted onto the UCNPs via a high-affinity molecular linker barstar:barnase (Bs:Bn) to allow their specific binding to the human epidermal growth factor receptor HER2/neu, which is overexpressed in human breast adenocarcinoma cells SK-BR-3. UCNP-Bs:Bn-scFv4D5 biocomplexes exhibited high-specific immobilization on the SK-BR-3 cells with the optical contrast as high as 10∶1 benchmarked against a negative control cell line. Breast cancer optical diagnostics was experimentally modeled by means of epi-luminescence imaging of a monolayer of the UCNP-labeled SK-BR-3 cells buried under a breast tissue mimicking optical phantom. The experimental results were analyzed theoretically and projected to in vivo detection of early-stage breast cancer. The model predicts that the UCNP-assisted cancer detection is feasible up to 4 mm in tissue depth, showing considerable potential for diagnostic and image-guided surgery applications.

A method for measuring refractive index n of nanosize particles in the visible and near-IR spectral ranges is proposed. The method is based on comparing refractive index n colloid of a colloid solution of nanoparticles in several solvents with refractive indices n solvent of corresponding pure solvents and has an accuracy of ±2 × 10 -4 . Upconversion nanosize phosphors (UCNPs) are synthesized in the form of a β-NaYF 4 crystalline matrix doped with Yb 3+ , Er 3+ , and Tm 3+ rare earth ions. UCNPs have a doped core with a diameter of 40 ± 5 nm and undoped shell with a thickness of 3-5 nm. Synthesized nanocrystals possess intense photoluminescence in the blue, green, and red spectral ranges upon excitation by IR radiation with a wavelength of 977 nm. Using a spectroscopic refractometer, the dispersion of the refractive index of β-NaYF 4 /Yb 3+ /Er 3+ /Tm 3+ nanocrystals was measured for the first time in the spectral range of 450-1000 nm with an accuracy of ±2 × 10 -4 .

Biocompatible PEG-containing UCNPs were designed for in vivo passive targeting of tumor associated with UCNP efficient accumulation and tumor contrast visualization.

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Recently introduced upconversion nanoparticles (UCNPs) have pushed the depth of photodynamic therapy (PDT) treatment to the centimetre range by converting deeply-penetrating near-infrared (NIR) radiation to visible radiation for photoexcitation of PDT drugs. Here we demonstrate that the direct exposure of the cancer tissue to phototoxic ultraviolet radiation generated by NIR-photoexcited UCNPs enabled successful PDT. To this aim, core/shell UCNPs of the formula NaYF:YbTm/NaYF featuring an enhanced band in the ultraviolet UV-A and UV-B spectral bands were rationally designed and synthesised. Coupling UCNPs to the recombinant modules of the Designed Ankyrin Repeat Protein (DARPin) fused to a fluorescent protein mCherry allowed the target delivery of DARPin-mCherry/UCNP to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2/neu receptors, as confirmed by fluorescence microscopy. DARPin-mCherry/UCNPs were demonstrated to be phototoxic to SK-BR-3 cells under 975 nm laser irradiation at a dose of 900 J cm due to the UV photoexcitation of endogenous photosensitizers and concomitant generation of reactive oxygen species. The Lewis lung cancer mouse model was employed to demonstrate the feasibility of PDT using UCNP-mediated UV excitation of endogenous photosensitizers in the tumor tissue at a NIR dose of 1200 J cm. This study paves the way for exploring and harnessing UV photoexcitation processes in deep tissues in vivo.