A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C60’s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox’s antiproliferative activity and C60’s photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60’s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment.
Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on Fe3O4/Au magneto-plasmonic nanocomposites (MPNC) synthesized with the use of amino acid tryptophan via chemical and photochemical reduction of Au ions in the presence of nanosized magnetite. The magnetic field (MF) induced aggregation was accompanied by an increase in the absorption in the near-infrared (NIR) spectral region, which was demonstrated to provide an enhanced photothermal (PT) effect under NIR laser irradiation (at 808 nm). A possibility for therapeutic application of the MPNC was illustrated using cancer cells in vitro. Cultured HeLa cells were treated by MPNC in the presence of MF and without it, following laser irradiation and imaging using confocal laser scanning microscopy. After scanning laser irradiation of the MPNC/MF treated cells, a formation and rise of photothermally-induced microbubbles on the cell surfaces was observed, leading to a damage of the cell membrane and cell destruction. We conclude that the synthesized magneto-plasmonic Fe3O4/Au nanosystems exhibit magnetic field-induced reversible aggregation accompanied by an increase in NIR absorption, allowing for an opportunity to magnetophoretically control and locally enhance a NIR light-induced thermal effect, which holds high promise for the application in photothermal therapy.
A thermosensitive polymeric nanoformulation (NF) was fabricated for thermally enhanced near-infrared (NIR) fluorescence imaging (FLI). It comprised core–shell nanoparticles (NPs) with a polystyrene core and a thermosensitive shell of a co-polymer of N-isopropylacrylamide and acrylamide [poly(NIPAM-co-AA)], which underwent a reversible conformational transition at 38–40 °C (corresponding to a lower critical solution temperature, LCST), leading to a reversible shrinkage of NPs from ∼250 nm to ∼140 nm for temperatures above LCST. The NIR dye 3782SL or photosensitizer HPPH were loaded to the NP shells. While the fluorescence of 3782SL and HPPH was quenched in water, it recovered in the NPs dispersion as a result of adsorption by NPs. Fluorescence for 3782SL and HPPH in NF increased when the temperature increased above LCST. Heating of HPPH-loaded NFs led to the elongation of the HPPH fluorescence lifetime and increased the generation of singlet oxygen (1O2). This occurred as a result of the NP shrinkage, corresponding shell compaction and NP aggregation, which hindered the internal conversion for photoexcited molecules adsorbed by NPs, and resulted in an increase in other deactivation pathways, namely fluorescence emission and intersystem crossing. The latter led to an increase in the triplet yield and, consequently, in singlet oxygen generation. Fluorescence microscopy revealed a 2–3-fold increase in the 3782SL or HPPH fluorescence signal from the NF-treated cells after they were heated up to 40 °C. Comparable results were obtained for the FLI of mice in vivo, after subcutaneous, intravenous, or intratumoral NF injections and localized heating by NIR (1.3 μm) laser irradiation. The developed NF holds immense potential for thermally enhanced FLI and photodynamic therapy.
15 July 2024 in Molecular Crystals and Liquid Crystals
The use of lasers in oncology is constantly evolving. In recent years, the mechanisms of the effect of laser radiation, particularly of the infrared spectrum, on tumour cells in combination with various chemotherapeutic agents have been studied. The aim. To study the effect of laser radiation with a wavelength of 660 and 810 nm on the survival of tumour cell cultures MCF7 and MCF7DOX in the presence of doxorubicin. Materials and methods. Tumour cells of MCF7 and MCF7DOX cultures were cultured in DMEM medium (Biowest, France) with 10 % fetal calf serum (FST) (Biowest, France) and 40 μg / ml gentamicin (Sigma, USA). Doxorubicin was added to the cells to a final concentration of 1 μg / ml. Cells were irradiated with a laser (Photonica-Plus, Ukraine) with a wavelength of 660 and 810 nm (irradiation time – 5 min, power density – 50 mV/cm2, irradiation dose 15 J/cm2). The results were recorded using a multiwell spectrophotometer (Labsystems Multiskan PLUS, Finland). Photomicrographs of cells were taken using a Carl Zeiss microscope, Germany. Results. Cell survival assessment and morphological characteristics in micropreparations indicate the antitumor efficacy of the combined effects of laser irradiation and doxorubicin. The most pronounced cytotoxic effect on MCF7-DOX culture cells was caused by doxorubicin exposure for 90 min in combination with infrared laser irradiation (λ=810 nm). Conclusions. Infrared laser light synergises with the toxic effects of doxorubicin and creates favourable conditions for apoptosis of tumour cells, as evidenced by cytomorphological data.