Fullerene C60 as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique phys

Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber’ low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C₆₀ fullerene (C₆₀). The complexation between C₆₀ and Ber molecules was evidenced with computer simulation. The aim of the present study was to estimate the effect of the free Ber and C₆₀-Ber nanocomplex in a low Ber equivalent concentration on Lewis lung carcinoma cells (LLC) invasion potential, expression of epithelial-to-mesenchymal transition (EMT) markers in vitro, and the ability of cancer cells to form distant lung metastases in vivo in a mice model of LLC. It was shown that in contrast to free Ber its nanocomplex with C₆₀ demonstrated significantly higher efficiency to suppress invasion potential, to downregulate the level of EMT-inducing transcription factors SNAI1, ZEB1, and TWIST1, to unblock expression of epithelial marker E-cadherin, and to repress cancer stem cells-like markers. More importantly, a relatively low dose of C₆₀-Ber nanocomplex was able to suppress lung metastasis in vivo. These findings indicated that сomplexation of natural alkaloid Ber with C₆₀ can be used as an additional therapeutic strategy against aggressive lung cancer.

Current research data on the biological effects of carbon nanoparticles (CNMs), such as C60 fullerene, graphene, graphene oxide, and single- and multiwalle

The powerful antioxidant properties of C₆₀ fullerenes have been widely used in biomedical nanotechnology. Owing to the negative effects of free radicals in oxidative stress processes, antioxidants are required to protect injured muscles. Here, the effect of water-soluble C₆₀ fullerenes (daily oral dose 1 mg kg⁻¹) on the process of restoration of contractile activity of skeletal muscle of rats (muscle gastrocnemius) 15 d after the initiation of open trauma of different severity was studied for the first time. The structural organization of C₆₀ fullerene nanoparticles in aqueous solution was analyzed by dynamic light scattering and atomic force microscopy techniques. Such biomechanical parameters of muscle gastrocnemius contraction as integrated muscle power, levels of generation of its maximum and minimum force, and time interval until reaching 50% of the level of force response of the muscle were analyzed. Such biochemical indices as concentrations of c-reactive protein, creatinine, and lactate in the rat blood, as well as indices of pro- and antioxidant balance (activities of superoxide dismutase and catalase, the concentration of reduced glutathione) in the blood and muscle tissue of experimental animals, were investigated. It was found that application of water-soluble C₆₀ fullerenes statistically significantly improves biomechanical parameters of contraction of injured muscle gastrocnemius at the level of 30–45 ± 3%, which is confirmed by normalization of biochemical indices in the blood and muscle tissue of rats at the level of 35–50 ± 3% and 20–37 ± 3%, correspondingly, relative to the open injury group. These findings open the possibility of using C₆₀ fullerenes as potential therapeutic nanoagents capable of correcting pathological states of the muscular system during the physiological repair of open injuries.

Introduction: C₆₀ fullerene has received great attention as a candidate for biomedical applications. Due to unique structure and properties, C₆₀ fullerene nanoparticles are supposed to be useful in drug delivery, photodynamic therapy (PDT) of cancer, and reversion of tumor cells’ multidrug resistance. The aim of this study was to elucidate the possible molecular mechanisms involved in photoexcited C₆₀ fullerene-dependent enhancement of cisplatin toxicity against leukemic cells resistant to cisplatin. Methods: Stable homogeneous pristine C₆₀ fullerene aqueous colloid solution (10-4 М, purity 99.5%) was used in the study. The photoactivation of C₆₀ fullerene accumulated by L1210R cells was done by irradiation in microplates with light-emitting diode lamp (420-700 nm light, 100 mW·cm-2). Cells were further incubated with the addition of Cis-Pt to a final concentration of 1 μg/mL. Activation of p38 MAPK was visualized by Western blot analysis. Flow cytometry was used for the estimation of cells distribution on cell cycle. Mitochondrial membrane potential (Δψ_m) was estimated with the use of fluorescent potential-sensitive probe TMRE (Tetramethylrhodamine Ethyl Ester). Results: Cis-Pt applied alone at 1 μg/mL concentration failed to affect mitochondrial membrane potential in L1210R cells or cell cycle distribution as compared with untreated cells. Activation of ROS-sensitive proapoptotic p38 kinase and enhanced content of cells in subG1 phase were detected after irradiation of L1210R cells treated with 10-5M C₆₀ fullerene. Combined treatment with photoexcited C₆₀ fullerene and Cis-Pt was followed by the dissipation of Δψ_m at early-term period, blockage of cell transition into S phase, and considerable accumulation of cells in proapoptotic subG1 phase at prolonged incubation. Conclusion: The effect of the synergic cytotoxic activity of both agents allowed to suppose that photoexcited C₆₀ fullerene promoted Cis-Pt accumulation in leukemic cells resistant to Cis-Pt. The data obtained could be useful for the development of new approaches to overcome drug-resistance of leukemic cells.

The remarkable antioxidant capabilities of biocompatible and safe C₆₀ fullerenes have extensive applications in biomedicine. This study is the first to present an investigation into the effect of water-soluble C₆₀ fullerenes on post-traumatic recovery of the muscle gastrocnemius in rats. Tensometry was used to investigate the biomechanical parameters of muscle contraction, specifically the times of reaching and holding the maximum force response of the muscle, and the return of muscle contraction force to the initial value after cessation of stimulation. Blood biochemical indicators were assessed, including concentrations of c-reactive protein, lactate, creatinine, and reduced glutathione, as well as superoxide dismutase and catalase activities 5, 10, and 15 days after initiating open muscle injury. Histopathological analysis was also performed to examine the rat muscle gastrocnemius damage on day 15 after the onset of injury. It was found that C₆₀ fullerenes reduced the stiffness of injured skeletal muscle, thereby slowing the development of fibrosis, and inhibiting the inflammatory process due to their antioxidant properties. There was also a reduction in histopathological features of muscle damage. These findings suggest using of carbon nanoparticles to correct pathological conditions that may occur during the physiological repair of damaged muscle tissues.