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1.  Surface plasmon resonance-induced photoactivation of gold nanoparticles as bactericidal agents against methicillin-resistant Staphylococcus aureus 
Systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other bacteria are responsible for millions of deaths worldwide, and much of this mortality is due to the rise of antibiotic-resistant organisms as a result of natural selection. Gold nanoparticles synthesized using the standard wet chemical procedure were photoexcited using an 808 nm 2 W laser diode and further administered to MRSA bacteria. Flow cytometry, transmission electron microscopy, contrast phase microscopy, and fluorescence microscopy combined with immunochemical staining were used to examine the interaction of the photoexcited gold nano-particles with MRSA bacteria. We show here that phonon–phonon interactions following laser photoexcitation of gold nanoparticles exhibit increased MRSA necrotic rates at low concentrations and short incubation times compared with MRSA treated with gold nanoparticles alone. These unique data may represent a step forward in the study of bactericidal effects of various nanomaterials, with applications in biology and medicine.
PMCID: PMC3968082  PMID: 24711697
MRSA; SPR; multi-drug resistant bacteria; infection; gold nanoparticles; laser
2.  Minimal Invasive Treatment of Abdominal Multiorgan Echinococcosis 
International Surgery  2013;98(1):61-64.
Hydatid disease is a severe zoonosis, exerting a high economic and social impact through its numerous complications, leading to disabilities, even death. Because of technical developments, especially the increasing experience of surgeons, laparoscopic surgery has been extended so that it can be successfully applied to abdominal hydatid cysts. We present the case of a 16-year-old patient who came to our clinic for upper abdominal pain. The abdominal ultrasonography and computed tomography (CT) showed 2 cyst-like tumors, with hydatid features: one affecting the eighth liver segment and the other located at the upper pole of the spleen. We performed the surgical intervention using a laparoscopic approach, with an uneventful postoperative follow-up and the patient was discharged home on postoperative day 4. The postoperative images at 6 and 12 months showed a decrease in size of the remnant cystic cavities.
PMCID: PMC3723166  PMID: 23438278
Hydatid cyst; Laparoscopic treatment; Abdominal echinococcosis; Partial pericystectomy
3.  Photothermal Treatment of Human Pancreatic Cancer Using PEGylated Multi-Walled Carbon Nanotubes Induces Apoptosis by Triggering Mitochondrial Membrane Depolarization Mechanism 
Journal of Cancer  2014;5(8):679-688.
Pancreatic cancer (PC) is one of the most lethal solid tumor in humans, with an overall 5-year survival rate of less than 5%. Thermally active carbon nanotubes have already brought to light promising results in PC research and treatment.
We report here the construct of a nano-biosystem based on multi-walled carbon nanotubes and polyethylene glycol (PEG) molecules validated through AFM, UV-Vis and DLS. We next studied the photothermal effect of these PEG-ylated multi-walled carbon nanotubes (5, 10 and 50 μg/mL, respectively) on pancreatic cancer cells (PANC-1) and further analyzed the molecular and cellular events involved in cell death occurrence. Using cell proliferation, apoptosis, membrane polarization and oxidative stress assays for ELISA, fluorescence microscopy and flow cytometry we show here that hyperthermia following MWCNTs-PEG laser mediated treatment (808 nm, 2W) leads to mitochondrial membrane depolarization that activates the flux of free radicals within the cell and the oxidative state mediate cellular damage in PC cells via apoptotic pathway. Our results are of decisive importance especially in regard with the development of novel nano-biosystems capable to target mitochondria and to synergically act both as cytotoxic drug as well as thermally active agents in order to overcome one of the most common problem met in oncology, that of intrinsic resistance to chemotherapeutics.
PMCID: PMC4174512  PMID: 25258649
carbon nanotubes; pancreatic cancer; PEG functionalization; photothermal ablation; apoptosis; mitochondrial therapy.
4.  Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin production in pancreatic beta cells via MIF pathway 
Recent data in the literature support the role of nicotinamide (NA) as a pharmacologic agent that stimulates pancreatic beta-cells to produce insulin in vitro. There are data showing that carbon nanotubes may be useful in initiating and maintaining cellular metabolic responses. This study shows that administration of multiwalled carbon nanotubes (MWCNTs) functionalized with nicotinamide (NA-MWCNTs) leads to significant insulin production compared with individual administration of NA, MWCNTs, and a control solution. Treatment of 1.4E7 cells for 30 minutes with NA-MWCNTs at concentrations ranging from 1 mg/L to 20 mg/L resulted in significantly increased insulin release (0.18 ± 0.026 ng/mL for 1 mg/L, 0.21 ± 0.024 ng/mL for 5 mg/L, and 0.27 ± 0.028 ng/mL for 20 mg/L). Thus, compared with cells treated with NA only (0.1 ± 0.01 ng/mL for 1 mg/L, 0.12 ± 0.017 ng/mL for 5 mg/L, and 0.17 ± 0.01 ng/mL for 20 mg/L) we observed a significant positive effect on insulin release in cells treated with NA-MWCNTs. The results were confirmed using flow cytometry, epifluorescence microscopy combined with immunochemistry staining, and enzyme-linked immunosorbent assay techniques. In addition, using immunofluorescence microscopy techniques, we were able to demonstrate that MWCNTs enhance insulin production via the macrophage migration inhibitory factor pathway. The application and potential of NA combined with MWCNTs as an antidiabetic agent may represent the beginning of a new chapter in the nanomediated treatment of diabetes mellitus.
PMCID: PMC3770514  PMID: 24039418
carbon nanotubes; NA; insulin-producing cells; insulin; macrophage migration inhibitory factor; diabetes mellitus
5.  Open or laparoscopic treatment for hydatid disease of the liver? A 10-year single-institution experience 
Surgical Endoscopy  2013;27(6):2110-2116.
Selection of the most appropriate treatment to obtain the lowest morbidity, mortality, and recurrence rates is mandatory for hydatid disease of the liver. This study evaluated the results of laparoscopic treatment (compared with the open approach) in the context of a 10-year single-institution experience.
Between January 1998 and January 2008, 333 patients with hydatid disease of the liver underwent surgery in the authors’ department. Only the following aspects were considered as selection criteria for laparoscopic surgery: liver cyst not located in segment 1 or 7, with corticalization on the surface and no evidence of intrabiliary rupture. Of 62 patients who underwent laparoscopic treatment, 3 required conversion to open surgery. The remaining 59 patients (group 1) were analyzed. During the same period, 271 patients with hepatic hydatid disease underwent conventional surgery, but only 172 records were compatible with the criteria for the laparoscopic approach and the respective patients were retrospectively reviewed (group 2).
Conversion to open surgery occurred in three cases (4.84 %). The mean cyst diameter was 6.62 cm (range, 2–15 cm) in group 1 and 7.23 cm (range, 2–18 cm) in group 2 (p = 0.699). The mean operative time was 72 min (range, 45–140 min) in group 1 and 65 min (range, 35–120 min) in group 2 (p < 0.001). The general complication rate and abdominal wound complication rate were respectively 0 % and 0 % in group 1 (p = 0.023) compared with 5.23 and 8.72 % in group 2 (p = 0.015). The mean hospital stay was 6.42 days (range, 1–21 days) in group 1 and 11.7 days (range, 4–80 days) in group 2 (p < 0.001). The mean follow-up period was 24.2 months (range, 6–32 months) in group 1 and 28.4 months (range, 6–40 months) in group 2. No recurrences were observed in either group during this period.
Laparoscopic surgery provides a safe and efficacious approach for almost all types of hepatic hydatid cysts. Large, prospective, randomized trials are needed to confirm its superiority.
PMCID: PMC3661041  PMID: 23370963
Hepatic hydatid cyst; Laparoscopic surgery; Treatment of hydatid disease
6.  Ethinylestradiol30μg-drospirenone and metformin: could this combination improve endothelial dysfunction in polycystic ovary syndrome? 
We are hereby investigating for the first time the effect of the association ethinylestradiol30μg-drospirenone 3mg (DRP/EE30μg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS).
25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI): 28.44 ± 6.23) who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30μg (21 days/month) and metformin (1700 mg daily) were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI > 25 kg/m2) were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD) on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry) and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention.
The combination between DRP/EE30μg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48 ± 1.00 vs FMD-PCOS6 months7.43 ± 1.04, p = 0.033), as well as body composition and insulin insensitivity (p < 0.05). Regarding hsCRP levels, there was no significant intragroup (PCOS6months – PCOSbasal) difference.
A 6-month course of metformin- DRP/EE30μg (associated with weight loss) improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors ( Identifier: NCT01459445).
PMCID: PMC3413550  PMID: 22713099
Ethinylestradiol30μg-drospirenone; Flow-mediated dilatation; Endothelial dysfunction; HsCRP; Metformin; Polycystic ovary syndrome
7.  Influence of nanomaterials on stem cell differentiation: designing an appropriate nanobiointerface 
During the last decade, due to advances in functionalization chemistry, novel nanobiomaterials with applications in tissue engineering and regenerative medicine have been developed. These novel materials with their unique physical and chemical properties are bioactive hierarchical structures that hold great promise for future development of human tissues. Thus, various nanomaterials are currently being intensively explored in the directed differentiation of stem cells, the design of novel bioactive scaffolds, and new research avenues towards tissue regeneration. This paper illustrates the latest achievements in the applications of nanotechnology in tissue engineering in the field of regenerative medicine.
PMCID: PMC3356220  PMID: 22619557
nanotechnology; nanomaterials; tissue engineering; regeneration; stem cell differentiation
8.  Advances in cancer therapy through the use of carbon nanotube-mediated targeted hyperthermia 
Carbon nanotubes (CNTs) are emerging versatile tools in nanomedicine applications, particularly in the field of cancer targeting. Due to diverse surface chemistry and unique thermal properties, CNTs can act as strong optical absorbers in near infrared light where biological systems prove to be highly transparent. The process of laser-mediated ablation of cancer cells marked with biofunctionalized CNTs is frequently termed “nanophotothermolysis.” This paper illustrates the potential of engineered CNTs as laser-activated photothermal agents for the selective nanophotothermolysis of cancer cells.
PMCID: PMC3160953  PMID: 21904457
carbon nanotubes; cancer targeting; functionalization; optical excitation; cancer treatment
9.  Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes 
The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called “nanophotothermolysis”. We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion.
PMCID: PMC3124855  PMID: 21720504
noncovalent functionalization; irradiation; tumor; malignant; MWCNTs
10.  Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin 
The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA–MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA–MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA–MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA–MWCNTs in a similar manner. Our results clearly show that HSA–MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.
PMCID: PMC3026578  PMID: 21289990
carbon nanotubes; albumin; HepG2 cells; noncovalent functionalization; laser irradiation; Gp60 receptor

Results 1-10 (10)