Characterization and Evaluation of Nano-niosomes Encapsulating Docetaxel against Human Breast, Pancreatic, and Pulmonary Adenocarcinoma Cancer Cell Lines.

Background: Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity. Objective: In this study, nano-niosomes were introduced for improving therapeutic index of DXL. Material and Methods: In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments. Results: DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20. Conclusion: Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.

Synchronized Chemotherapy/Photothermal Therapy/Sonodynamic Therapy of Human Triple-Negative and Estrogen Receptor-Positive Breast Cancer Cells Using a Doxorubicin-Gold Nanoclusters-Albumin Nanobioconjugate.

OBJECTIVE: Novel strategies for treating triple-negative breast cancer (TNBC) are ongoing because of the lack of standard-of-care treatment. Nanoframed materials with a protein pillar are considered a valuable tool for designing multigoals of energy-absorbing/medication cargo and are a bridge to cross-conventional treatment strategies. METHODS: Nanobioconjugates of gold nanoclusters-bovine serum albumin (AuNCs-BSA) and doxorubicin-AuNCs-BSA (Dox-AuNCs-BSA) were prepared and employed as a simultaneous double photosensitizer/sonosensitizer and triple chemotherapeutic/photosensitizer/sonosensitizer, respectively. RESULTS: The highly stable AuNCs-BSA and Dox-AuNCs-BSA have ζ potentials of -29 and -18 mV, respectively, and represent valuable photothermal and sonodynamic activities for the combination of photothermal therapy and sonodynamic therapy (PTT/SDT) and synchronized chemotherapy/photothermal therapy/sonodynamic therapy (CTX/PTT/SDT) of human TNBC cells, respectively. The efficiency of photothermal conversion of AuNCs-BSA was calculated to be a promising value of 32.9%. AuNCs-BSA and Dox-AuNCs-BSA were activated on either laser light irradiation or ultrasound exposure with the highest efficiency on the combination of both types of radiation. CTX/PTT/SDT of MCF-7 and MDA-MB-231 breast cancer cell lines by Dox-AuNCs-BSA were evaluated with the MTT cell proliferation assay and found to progress synergistically. CONCLUSION: Results of the MTT assay, detection of the generation of intracellular reactive oxygen species and occurrence of apoptosis in the cells confirmed that CTX/PTT/SDT by Dox-AuNCs-BSA was attained with lower needed doses of the drug and improved tumor cell ablation, which would result in the enhancement of therapeutic efficacy and overcoming of therapeutic resistance.

A Study of Sonodynamic Therapy of Melanoma C540 Cells in Vitro by Titania/Gold Nanoparticles.

Background: Sonodynamic Therapy (SDT), a safe and non-invasive strategy in tumor therapy, is in development using novel sono-sensitizers, activated by low-intensity ultrasound radiation. SDT mainly progresses through Reactive Oxygen Species (ROS) generation followed by cell annihilation. Objective: The current study aimed to investigate the effect of ultrasound therapy with titania/gold nanoparticles (NPs) on melanoma cancer. Material and Methods: In this experimental study, Titania/gold NPs (TGNPs) were synthesized, and their activity was investigated in sonodynamic therapy of a melanoma cancer cell line (C540). SDT was performed at 1.0 W cm-2 and 1.0 MHz for one minute. Results: The synthesized NPs that comprised gold NPs of <10 nm into titania NPs of <20 nm showed great stability and cytocompatibility. While TGNPs were biocompatible, a remarkable rate of cell ablation was observed upon ultrasound irradiation due to ROS generation. Conclusion: The SDT using TGNPs can be introduced as an alternative and low-cost treatment method for melanoma malignancy.

Pulsed sonodynamic therapy of melanoma cancer cells using nanoparticles of and mesoporous platinum.

OBJECTIVE: Noble metal nanomaterials have been introduced as ideal sonosensitizers for sonodynamic therapy (SDT) of cancer. In this research, platinum nanoparticles (PtNPs) and mesoporous platinum (MPt) were first synthesized and then evaluated as novel sonosensitizers. METHODS: Ultrasound waves were radiated at two different power densities and two different pulse ratios to develop a pulsed radiation route for SDT of the malignant melanoma cell line C540 (B16/F10). Fluorescence emission was recorded as an indicator of intracellular reactive oxygen generation during the treatment. RESULTS: Platinum nanoparticles had an average diameter of 12 ± 7 nm and a zeta potential of -17.6 mV; also, MPt had a sponge-like and highly porous structure with a pore size <11 nm and a zeta potential of -39.5 mV. Both PtNPs and MPt, particularly the latter, enhanced the rate of inhibition of tumor cell growth on ultrasound radiation at an output power density of 1.0 W cm-2 and pulse ratio of 30% over 10 min without intensifying temperature. CONCLUSION: Use of the developed pulsed (rather than continuous) radiation in SDT and PtNPs or MPT, without hyperthermia, resulted in a new effective cancer treatment method based on the mechanisms of cavitation and/or ROS generation.

Fractionated Sonodynamic Therapy Using Gold@Poly(ortho-aminophenol) Nanoparticles and Multistep Low-Intensity Ultrasound Irradiation to Treat Melanoma Cancer: In Vitro and In Vivo Studies.

OBJECTIVE: Cancer treatment using ultrasound irradiation with low intensities along with a sonosensitizer has been found to have significant advantages, such as high penetration depth in tissues, non-invasive therapeutic character, minor side effects, good patient adherence and preferential tumor area treatment. In the present study, gold nanoparticles covered by poly(ortho-aminophenol) (Au@POAP NPs) were synthesized and characterized as a new sonosensitizer. METHODS: We investigated Au@POAP NPs efficacy on fractionated ultrasound irradiation for treatment of melanoma cancer in vitro as well as in vivo. DISCUSSION: In vitro examinations revealed that although Au@POAP NPs (with a mean size of 9.8 nm) alone represented concentration-dependent cytotoxicity against the B16/F10 cell line, multistep ultrasound irradiation (1 MHz frequency, 1.0 W/cm2 intensity, 60 s irradiation time) of the cells in the attendance of Au@POAP NPs led to efficient cell sonodynamic therapy (SDT) and death. Histological analyses revealed that in vivo fractionated SDT toward melanoma tumors of male balb/c mice led to no residual viable tumor cell after 10 d. CONCLUSION: A deep sonosensitizing effectiveness of Au@POAP NPs on fractionated low-intensity ultrasound irradiation was attained with the main mechanism of tumor cell eradication of promotion of apoptosis or necrosis through dramatically increased reactive oxygen species levels.

Effects of labeling human mesenchymal stem cells with superparamagnetic zinc-nickel ferrite nanoparticles on cellular characteristics and adipogenesis/osteogenesis differentiation.

OBJECTIVE: An attractive cell source for stem cell-based therapy are WJ-MSCs. Hence, tracking WJ-MSCs using non-invasive imaging procedures (such as MRI) and contrast agents (Zn0.5Ni0.5Fe2O4, NFNPs) are required to evaluate cell distribution, migration, and differentiation. RESULTS: Results showed that the bare and dextrin-coated NFNPs were internalized inside the WJ-MSCs and had no effect on the cell viability, proliferation, apoptosis, karyotyping, and morphology of WJ-MSCs up to 125 µg/mL. Besides, treated WJ-MSCs were differentiated into osteo/adipocyte-like cells. The expression of RUNX 2, SPP 1 (P < 0.05), and OCN (P > 0.05) genes in the WJ-MSCs treated with dextrin-coated NFNPs was higher than the untreated WJ-MSCs; and the expression of CFD, LPL, and PPAR-γ genes was reduced in WJ-MSCs treated with both NFNPs in comparison with the untreated WJ-MSCs (P > 0.05). CONCLUSION: Overall, results showed that dextrin-coated NFNPs had no adverse effect on the cellular characteristics, proliferation, and differentiation of WJ-MSCs, and suggesting their potential clinical efficacy.

Development of a Composite of Polypyrrole-Coated Carbon Nanotubes as a Sonosensitizer for Treatment of Melanoma Cancer Under Multi-Step Ultrasound Irradiation.

Sonodynamic therapy (SDT) has established a novel route for treating solid cancers. Low-intensity ultrasound irradiation accompanied by a sonosensitizer has revealed remarkable advantages for cancer therapy such as targeted uptake, access to deeper tumors, insignificant side effects and invasiveness, compared with other therapeutic methods. In this study, we scrutinized synthesis and characterization of a polypyrrole-coated multi-walled carbon nanotubes composite (PPy@MWCNTs). PPy@MWCNTs can absorb ultrasound irradiation by both of its components, and it was introduced as a new sonosensitizer. The composite was characterized by field emission scanning electron microscopy (FESEM), and its ability to temperature elevation was explored. FESEM images revealed that PPy@MWCNTs comprised nanotubes of 36.3 ± 5.1 nm in diameter with up to several micrometer in length. Ultrasound irradiation at 1 MHz and 1.0 W cm-2 for 60 s in four steps led to an efficient SDT in vitro (16.3 ± 2.8°C temperature increment for 250 µg mL-1 of PPy@MWCNTs), in C540 (B16/F10) cell line and a melanoma tumor model in male balb/c mice. In vitro examinations revealed that PPy@MWCNTs represented a concentration-dependent cytotoxicity on multi-step ultrasound irradiation (a cell viability of 8.9% for 250 µg mL-1 of PPy@MWCNTs). Histologic analyses and tumor volume decrement after 10 d revealed detrimental SDT effects of PPy@MWCNTs on tumors (75% necrosis and 50% decrement in tumor volume). Thermal effects and reactive oxygen species generation were the reasons of the working function of PPy@MWCNTs in SDT.

Photothermal inactivation of methicillin-resistant Staphylococcus aureus: anti-biofilm mediated by a polypyrrole-carbon nanocomposite.

Widespread resistance to antibiotics amongst pathogens has become a tremendous challenge of high morbidity and mortality rates which increases the needs to exploring novel methods of treatment. An efficient antimicrobial procedure to root out pathogenic bacteria is photothermal therapy. In this study, antimicrobial effects of a polypyrrole-carbon nanocomposite (PPy-C) upon laser irradiation in order to destroy the pathogenic gram-positive bacterium, methicillin-resistant Staphylococcus aureus (MRSA) were assessed. The bacterial cells were incubated with 500, 750 and 1000 µg ml-1 concentrations of PPy-C and irradiated with an 808-nm laser at a power density of 1.0 W cm-2. To indicate the biocompatibility and toxic effect of the nanocomposite without and with laser irradiation, the authors counted the number of CFUs and compared it to an untreated sample. Antibacterial mechanisms of PPy-C were assessed through temperature increment, reactive oxygen species production, and protein and DNA leakages. Photothermal heating assay showed that 26°C temperature increases in the presence of 1000 µg ml-1 PPy-C led to >98% killing of MRSA. Furthermore, 20 min radiation of near-infrared light to PPy-C in different concentrations indicated destruction and reduction in the MRSA biofilm formation. Therefore, PPy-C was introduced as a photothermal absorber with a bactericidal effect in MRSA.

A signal-on built in-marker electrochemical aptasensor for human prostate-specific antigen based on a hairbrush-like gold nanostructure.

A green electrodeposition method was firstly employed for the synthesis of round hairbrush-like gold nanostructure in the presence of cadaverine as a size and shape directing additive. The nanostructure which comprised of arrays of nanospindles was then applied as a transducer to fabricate a signal-on built in-marker electrochemical aptasensor for the detection of human prostate-specific antigen (PSA). The aptasensor detected PSA with a linear concentration range of 0.125 to 128 ng mL-1 and a limit of detection of 50 pg mL-1. The aptasensor was then successfully applied to detect PSA in the blood serum samples of healthy and patient persons.

Effect of Magnetic Fluid Hyperthermia on Implanted Melanoma in Mouse Models.

BACKGROUND: Nowadays, magnetic nanoparticles (MNPs) have received much attention because of their enormous potentials in many fields such as magnetic fluid hyperthermia (MFH). The goal of hyperthermia is to increase the temperature of malignant cells to destroy them without any lethal effect on normal tissues. To investigate the effectiveness of cancer therapy by magnetic fluid hyperthermia, Fe0.5Zn0.5Fe2O4 nanoparticles (FNPs) were used to undergo external magnetic field (f=515 kHz, H=100 G) in mice bearing implanted tumor. METHODS: FNPs were synthesized via precipitation and characterized using transmission electron microscopy (TEM), vibrating sample magnetometer, and Fourier transform infrared. For in vivo study, the mice bearing implanted tumor were divided into four groups (two mice per group), namely, control group, AMF group, MNPs group, and MNPs&AMF group. After 24 hours, the mice were sacrificed and each tumor specimen was prepared for histological analyses. The necrotic surface area was estimated by using graticule (Olympus, Japan) on tumor slides. RESULTS: The mean diameter of FNPs was estimated around 9 nm by TEM image and M versus H curve indicates that this particle is among superparamagnetic materials. According to histological analyses, no significant difference in necrosis extent was observed among the four groups. CONCLUSION: FNPs are biocompatible and have a good size for biomedical applications. However, for MFH approach, larger diameters especially in the range of ferromagnetic particles due to hysteresis loss can induce efficient heat in the target region.

Nanoporous nickel microspheres: synthesis and application for the electrocatalytic oxidation and determination of acyclovir.

Nickel microspheres were synthesized via a water-in-oil reverse nanoemulsion system using nickel nitrate as the nickel precursor and hydrazine hydrate as the reducing agent. The nanoemulsion was a triton X-100/cyclohexane/water ternary system. The surface morphology of the nickel microspheres was studied by scanning electron microscopy, which indicated that the microspheres had a nanoporous structure. The electrochemical behavior of the nanoporous nickel microspheres were studied in alkaline solution and were then employed to fabricate a modified carbon paste electrode in order to investigate the electrocatalytic oxidation of the drug acyclovir. The oxidation process involved, and its kinetics were investigated using cyclic voltammetry and chronoamperometry. The rate constant of the catalytic oxidation of acyclovir and the electron-transfer coefficient are reported. A sensitive, simple and time-saving amperometric procedure was developed for the analysis of acyclovir. The proposed amperometric method was also applied to determine acyclovir in tablets and topical cream.