Photothermal/sonodynamic therapy of melanoma tumor by a gold/manganese dioxide nanocomposite: In vitro and in vivo studies.

Nanosized materials have favorable applications in nanomedicine including photothermal therapy (PTT) and sonodynamic therapy (SDT) of most malignancies. Since conventional methods of cancer treatment encounter limitations, development of other efficient routes is quite necessary. In this study, a gold/manganese dioxide nanocomposite (Au/MnO2 NC) was synthesized as a novel photo- and sono- responsive nanomaterial that was activated upon laser light of 808-nm wavelength irradiation or ultrasound exposure for cancer treatment applications. The synthesized nanocomposite comprised gold nanoparticles of about 125 ±â€¯66 nm in diameter adhered to manganese dioxide nanoroads of 77 ±â€¯30 nm in diameter and up to 2 µm length. Au/MnO2 NC represented a very good photothermal and sonodynamic conversion ability. Cytotoxicity of Au/MnO2 NC toward the C540 (B16/F10) cell line was evaluated through thermal ablation and reactive oxygen species (ROS) generation upon phototherapy and sonotherapy, respectively. Intratumoral injection of a low-dose of Au/MnO2 NC into a melanoma tumor-bearing animal model followed by laser and ultrasound radiation led to necrosis in the tumor tissue. The findings revealed that Au/MnO2 NC is aphotosensitizer/sonosensitizer for PTT and SDT of cancer.

The Effects of Cold Preservation Solutions Supplemented with UDCA and α-Lipoic Acid on the Viability and Function of Isolated Human Hepatocytes.

BACKGROUND: Liver transplantation is the only treatment for end-stage and genetic liver diseases. The main burden of this treatment is the shortage of both living and cadaveric liver donors. An alternative treatment is using liver cell transplantation, which can be obtained from unused livers for transplantation. These hepatocytes should be kept ready in viable and functional situation in a frozen state to be instantly used when they would be needed. In our previous experience, we had isolated hepatocytes from unused livers. OBJECTIVE: To find a preserving solution for increasing viability and function of the isolated hepatocytes that are stored to be transplanted. METHODS: 9 cadaveric donor livers, which were not used for transplantation due to various causes such as severe steatosis, were selected to isolate hepatocytes. Various cold storage solutions were tried to find the best temperature for more viability and functionality for preservation of hepatocytes. University of Wisconsin (UW) solution and Williams E media were used as control media. 2 anti-apoptotic and anti-oxidative solutions, i.e., α-lipoic acid and ursodeoxycholic acid (UDCA), were used as cold preservatives solutions. The numbers of viable hepatocytes were estimated by trypan blue method; the functionality was assessed by the cells ability to produce urea. RESULTS: The highest number of viable and functional hepatocytes was obtained from freshly isolated cells. However, after preservation, the number of these viable hepatocytes and their functionality were not significantly different in cold storage solutions comparing to the control media used. Functionality of the isolated hepatocytes stored in UW with and without UCDA solution was similar to freshly isolated hepatocytes. CONCLUSION: Preservatives with anti-apoptotic and antioxidant activity could not increase the number of viable hepatocytes. Functionality of cold storing hepatocytes could be preserved similar to freshly isolated hepatocytes by UW solution with and without UCDA.

Repression of melanoma tumor in vitro and in vivo by photothermal effect of carbon xerogel nanoparticles.

Nanosized carbonaceous materials are favorable in biomedicine applications including photothermal therapy (PTT) of cancer. Since conventional strategies of cancer treatment have not responded to this serious disease, development of efficient alternative and promising strategies is highly desirable. In this study, carbon xerogel nanoparticles (CX-NPs) were synthesized as a novel photothermal nanomaterial and activated upon laser light of 808-nm wavelength for cancer phototherapy application. The synthesized CX-NPs had a spherical shape with a size of about 16 nm that showed nice photothermal conversion ability. Upon light irradiation with a power density of 1.0 W cm-2 for 15 min, a temperature increment occurred. A concentration-dependent cytotoxicity was also obtained for CX-NPs toward the C540 (B16/F10) cell line upon light irradiation, while CX-NPs presented biocompatibility in the mice model in dark. Photothermal property of CX-NPs efficiently led to reduction in the cell viability. A low-dose of CX-NPs was also applied in PTT of a melanoma tumor-bearing animal model. Based on tumor histopathological evaluations and volume change measurements in mice, a very good control of tumor situations after PTT by CX-NPs was attained. The findings revealed that CX-NPs is a good and novel photoabsorber for PTT of cancer.

Evaluation of a self-nanoemulsifying docetaxel delivery system.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.

In vitro and in vivo tumor annihilation by near-infrared photothermal effect of a NiFe2O4/C nanocomposite.

Nanothechnology-mediated photothermal therapy (PTT) is emerging as one of the inspiring alternative modality of cancer therapy that applies near-infrared radiation. High favorability of this approach is due to its minimum invasiveness, safety of non-targeted area, quick recovery, and capable simultaneous imaging. In this approach, photoabsorbing nanomaterials convert energy of infrared light to vibrational motion and generate heat. In the present study, a nanocomposite comprised nickel ferrite and carbon (NiFe2O4/C) was synthesized, characterized and introduced as a novel photoabsorbing agent in cancer phototherapy. NiFe2O4/C was characterized by field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction patterns. A diode laser of 808 nm with a power density of 1.0 W cm-2 was selected as the light source to evaluate the photothermal property of NiFe2O4/C toward cancer repression in C540 (B16/F10) cell line and melanoma bearing tumor model in male balb/c mice. Temperature enhancement ability of NiFe2O4/C confirmed its photoabsorbing property. While NiFe2O4/C had a concentration dependent cytotoxicity on C540 (B16/F10) cell line, PTT of NiFe2O4/C activated by laser irradiation showed its destroying effect on the C540 (B16/F10) cell line. On the other hand, histological analyses and tumor volume changes were performed for the in vivo PTT of NiFe2O4/C upon intratumoral injection. The results showed that after 24 h, PTT of the nanocomposite cured the tumor properly, whereas NiFe2O4/C injection or laser exposure alone had no treatment effect. Also, 5-day post-treating the melanoma bearing tumor model indicated that the level of necrosis significantly increased during this time in the PTT treated mouse. Therefore, PTT using NiFe2O4/C is proposed as a promising procedure for the melanoma cancer therapy.

Evaluation of a nanocomposite of PEG-curcumin-gold nanoparticles as a near-infrared photothermal agent: an in vitro and animal model investigation.

Hyperthermia is a promising alternative modality for the conventional cancer treatments. Nanoparticle-mediated photothermal therapy (PTT) has been widely applied for hyperthermia cancer therapy by a near-infrared light irradiation. Some special nanoparticles can convert light energy into heat and destroy the tumor cells. Inspired from the photothermal efficacy of the gold nanoparticles, here we synthesized, characterized, and applied novel photothermal polyethylene glycol-curcumin-gold nanoparticles (PEG-Cur-Au NPs) in cancer PTT. The effect of PEG-Cur-Au NPs upon irradiation by an 808-nm laser on C540 (B16/F10) cell line as well as implanted (bearing) melanoma tumor in inbred C57 mice was investigated. In vitro temperature increment, cell viability evaluation, and histological analyses were performed. The results showed a dose-dependent cytotoxicity of PEG-Cur-Au NPs toward C540 (B16/F10) cell line at concentrations ≥ 25 µg mL-1 with an IC50 value of 42.7 µg mL-1 in dark (and with no toxicity for 10 µg mL-1). On the other hand, 808-nm laser irradiation alone (without using PEG-Cur-Au NPs) for 10 min induced killing effect on the C540 (B16/F10) cell line in a laser power-dependent manner at power density > 0.5 W cm-2 (no toxicity for 0.5 W cm-2). However, PPT using PEG-Cur-Au NPs was tremendously observed after laser illumination. Even under laser irradiation at a power density of 0.5 W cm-2 of PEG-Cur-Au NPs of concentrations < 10 µg mL-1, PTT of the cells was substantial. Histological analyses and volume measurements of the induced tumors in the mice revealed an appropriate control of the tumors upon PTT by PEG-Cur-Au NPs. Combination of PEG-Cur-Au NP administration and 808-nm diode laser irradiation destroyed the melanoma cancer cells in the animal model.

Investigation of amyloid formation inhibition of chemically and biogenically from Citrus aurantium L. blossoms and Rose damascena oils of gold nanoparticles: Toxicity evaluation in rat pheochromocytoma PC12 cells.

Fibrillation inhibition effects of chemically and biogenically gold nanoparticles (GNPs) were investigated in vitro using human insulin as a model for fibrillation of protein. This inspection was followed using the Congo red assay, thioflavin T fluorescence measurements, transmission electron microscopy, and evaluation of cytotoxicity effects on rat pheochromocytoma PC12 cells. Biogenic GNPs were synthesized using oil extracts of Citrus aurantium L. blossoms and Rose damascena blossoms as reducing and concomitant agents. Congo red assay showed development of fibril formation of insulin at acidic media at 60°C over a period of 48h. In these circumstances, transmission electron micrographs confirmed the progress of fibril state from globular chains to amyloid. However, the results of ThT fluorescence measurements indicated a concentration-dependent inhibiting effect of chemically synthesized GNPs on insulin fibrillation in vitro, simultaneously by conversion of the formed fibrils into amorphous aggregates. Furthermore, biogenic GNPs were found to more effectively inhibit the fibril formation, compared to chemically synthesized GNPs. Accordingly, just 0.05nmolL-1 of the biogenic GNPs showed similar inhibition property of chemically synthesized GNPs with a concentration of 10nmolL-1. Both types of GNPs diminished toxicity of insulin fibrils in rat pheochromocytoma PC12 cells viability.