Several biochemical mechanisms, including the arachidonic acid cascade and activation of nicotinic acetylcholine receptors (nAChRs), are involved in increased tumor survival. Combined application of inhibitors acting on these two pathways may result in a more pronounced antitumor effect. Here, we show that baicalein (selective 12-lipoxygenase inhibitor), nordihydroguaiaretic acid (non-selective lipoxygenase inhibitor), and indomethacin (non-selective cyclooxygenase inhibitor) are cytotoxic to Ehrlich carcinoma cells in vitro. Marine snail α-conotoxins PnIA, RgIA and ArIB11L16D, blockers of α3β2/α6β2, α9α10 and α7 nAChR subtypes, respectively, as well as α-cobratoxin, a blocker of α7 and muscle subtype nAChRs, exhibit low cytotoxicity, but enhance the antitumor effect of baicalein 1.4-fold after 24 h and that of nordihydroguaiaretic acid 1.8–3.9-fold after 48 h of cell cultivation. α-Conotoxin MII, a blocker of α6-containing and α3β2 nAChR subtypes, increases the cytotoxic effect of indomethacin 1.9-fold after 48 h of cultivation. In vivo, baicalein, α-conotoxins MII and PnIA inhibit Ehrlich carcinoma growth and increase mouse survival; these effects are greatly enhanced by the combined application of α-conotoxin MII with indomethacin or conotoxin PnIA with baicalein. Thus, we show, for the first time, antitumor synergism of α-conotoxins and arachidonic acid cascade inhibitors.

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Here, we studied the effect of calcium ions on the physicochemical properties and cellular uptake of CdSe/ZnS quantum dots encapsulated with poly(maleic anhydride-alt-1-tetradecene), modified to a varying extent by quaternary ammonium groups. It was shown that quantum dots carrying negatively charged carboxyl groups in the polymer shell change their physicochemical and optical characteristics in the presence of Ca2+ and Ba2+ ions. As the negatively charged carboxyl groups in the shell are completely replaced by positively charged quaternary ammonium groups, these effects gradually decrease. A change in the physicochemical properties of nanoparticles leads to a change in their cellular uptake in the presence of calcium ions. Nanoparticles carrying only negatively charged groups in the shell in the presence of Ca2+ agglomerate and form conglomerates of nanoparticles and cells. The positively charged quaternary ammonium groups in the polymer shell of the nanoparticles increase their aggregative stability in the presence of Ca2+ and contribute to their uptake by cells. The mechanisms of uptake depend on nanoparticle’s charge. Nanoparticles with a positive ζ potential are absorbed by calcium-dependent mechanisms, which are suppressed by inhibition of the calcium-dependent enzyme dynamin or in the presence of calcium chelator EGTA. The uptake of nanoparticles with a negative ζ potential, in contrast, is enhanced by the chelation of calcium ions. This indicates the different role of cellular calcium-dependent mechanisms in the uptake of positively and negatively charged nanoparticles.

Since CdSe nanoplatelets were reported to have a ten-fold higher two-photon (2P) absorption coefficient as compared to quantum dots, we examined their applicability for cell labeling and 2P imaging. CdSSe/ZnCdS core-shell nanoplatelets and CdSe/ZnS quantum dots, both emitting at 585 nm were encapsulated with an amphiphilic zwitterionic polymer having slightly positive zeta potential. As measured with flow cytometry, glioma C6 cells demonstrated equally efficient uptake of nanoplatelets and quantum dots, despite the different sizes of these two types of nanoparticles. 2P fluorescence microscopy revealed ca. two orders of magnitude higher fluorescence response from nanoplatelets thus offering a chance to use them as highly efficient 2P fluorescent labels in biomedicine.

A comparative analysis of structural organization changes in skin microcirculatory vessels, serum level of leptin, diponectin, resistin in the ase of metabolic syndrome and doxorubicin intoxication was performed. It was shown that hypertrophy of the muscle fibers, perivascular space edema, and skin arteriole spasm in the metabolic syndrome accompanied by a structural reorganization of the organs and their vessels by the type of dystrophy. In the case of doxorubicin intoxication, the alteration processes were dominant. Changes in the level of hormones leptin adiponectin and resistin in the metabolic syndrome and doxorubicin intoxication were multidirectional.