RESUMO
PURPOSE: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments. METHODS: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs. RESULTS: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced. CONCLUSION: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.
Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Portadores de Fármacos/química , Melanoma/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular , Dacarbazina/administração & dosagem , Dacarbazina/farmacocinética , Composição de Medicamentos/métodos , Células Endoteliais , Humanos , Isoindóis/administração & dosagem , Isoindóis/farmacocinética , Masculino , Melanoma/patologia , Camundongos , Nanopartículas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacocinética , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Poliésteres/química , Álcool de Polivinil/química , Neoplasias Cutâneas/patologia , Distribuição Tecidual , Compostos de Zinco/administração & dosagem , Compostos de Zinco/farmacocinéticaRESUMO
Silver selenide (Ag2Se) is a promising nanomaterial due to its outstanding optoelectronic properties and countless bio-applications. To the best of our knowledge, we report, for the first time, a simple and easy method for the ultrasound-assisted synthesis of Ag2Se nanoparticles (NPs) by mixing aqueous solutions of silver nitrate (AgNO3) and selenous acid (H2SeO3) that act as Ag and Se sources, respectively, in the presence of dissolved fructose and starch that act as reducing and stabilizing agents, respectively. The concentrations of mono- and polysaccharides were screened to determine their effect on the size, shape and colloidal stability of the as-synthesized Ag2Se NPs which, in turn, impact the optical properties of these NPs. The morphology of the as-synthesized Ag2Se NPs was characterized by transmission electron microscopy (TEM) and both α- and ß-phases of Ag2Se were determined by X-ray diffraction (XRD). The optical properties of Ag2Se were studied using UV-Vis spectroscopy and its elemental composition was determined non-destructively using scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS). The biological activity of the Ag2Se NPs was assessed using cytotoxic and bactericidal approaches. Our findings pave the way to the cost-effective, fast and scalable production of valuable Ag2Se NPs that may be utilized in numerous fields.
Assuntos
Antibacterianos/química , Antineoplásicos/química , Nanopartículas Metálicas/química , Compostos de Selênio/química , Compostos de Prata/química , Açúcares/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Química Verde , Humanos , Polissacarídeos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Ácido Selenioso/química , Semicondutores , Nitrato de Prata/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
The fresh water microalga Chlamydomonas reinhardtii bioreduced Ag⺠to silver nanoparticles (AgNPs) via three biosynthetic routes in a process that could be a more sustainable alternative to conventionally produced AgNPs. The AgNPs were synthesized in either the presence of whole cell cultures, an exopolysaccharide (EPS)-containing cell culture supernatant, or living cells that had been separated from the EPS-containing supernatant and then washed before being suspended again in fresh media. While AgNPs were produced by all three methods, the washed cultures had no supernatant-derived EPS and produced only unstable AgNPs, thus the supernatant-EPS was shown to be necessary to cap and stabilize the biogenic AgNPs. TEM images showed stable AgNPs were mostly spherical and showed a bimodal size distribution about the size ranges of 3.0 ± 1.3 nm and 19.2 ± 5.0 nm for whole cultures and 3.5 ± 0.6 nm and 17.4 ± 2.6 nm for EPS only. Moreover, selected area electron diffraction pattern of these AgNPs confirmed their polycrystalline nature. FTIR of the as-produced AgNPs identified polysaccharides, polyphenols and proteins were responsible for the observed differences in the AgNP stability, size and shape. Additionally, Raman spectroscopy indicated carboxylate and amine groups were bound to the AgNP surface.
Assuntos
Chlamydomonas reinhardtii/química , Nanopartículas Metálicas/química , Prata/química , Biotecnologia , Química Verde , NanotecnologiaRESUMO
Silver Nanoparticles (AgNPs) are well known for applications in electronics and as antimicrobial agents because of their unique optical, electrical, cytotoxic and thermal properties. These nanoparticles can be synthesized via a wide variety of techniques; however, they require the use of hazardous solvents which have very high environmental impacts. Nanoscience researchers have attempted novel synthesis routes that reduce resource requirements and use benign chemicals, while maintaining control over their unique properties. The present study evaluates the potential environmental impacts of one such benign method using Life Cycle Assessment (LCA) techniques which are used to assess the environmental impacts of a product's life through all the stages from raw material extraction to disposal/ recycling. This research evaluates AgNPs which were synthesized using glucose as the reducing agent and food grade corn starch as the stabilizing agent in a microwave-assisted reaction system. GaBi 6.0 software was used to carry out the Life Cycle Impact Assessment on a declared unit of 1â¯kg of 3.0⯱â¯1.2â¯nm diameter AgNPs. The results indicate that the impacts are predominantly on acidification (AP), human health particulate air (HHAP) and human toxicity non-cancer (HTNCP) potentials. These impacts are mainly from the production of silver metal and electricity used. The starch and glucose used to produce AgNPs of 3.0⯱â¯1.2â¯nm is shown to have negligible environmental impacts and is therefore considered to be environmentally benign.