RESUMO
The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated "hot" NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance.
Assuntos
Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ouro/química , Ouro/farmacologia , Nanomedicina , Nanoestruturas , Fototerapia , Animais , Transformação Celular Viral , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Cinética , Lasers , CamundongosRESUMO
AIM: To develop new methodologies for selective cell ablation in a temporally and spatially precise fashion in model organisms. MATERIALS & METHODS: living polyps (Hydra vulgaris) treated with gold nanoprisms were near-infrared (NIR) irradiated and the photothermal effects evaluated at whole-animal, cellular and molecular levels. RESULTS: Nanoprisms showed good efficiency of internalization in living specimens, with no sign of toxicity; under NIR irradiation they induced cell death and the overexpression of the hsp70 gene. CONCLUSION: gold nanoprisms could be employed as efficient heat mediators in model organisms, and NIR-triggered cell ablation may represent a new advanced tool to study cell function. Solving bioethical and economical issues, invertebrates may provide alternative models bridging the gap between cell research and preclinical studies of photothermal therapy.
Assuntos
Ouro/administração & dosagem , Hydra/efeitos dos fármacos , Hipertermia Induzida , Nanopartículas Metálicas/administração & dosagem , Técnicas de Ablação , Animais , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Ouro/efeitos adversos , Proteínas de Choque Térmico HSP70/biossíntese , Humanos , Nanopartículas Metálicas/efeitos adversosRESUMO
Too hot to handle: The surroundings of magnetic nanoparticles can be heated by applying a magnetic field. Polymer-coated magnetic nanoparticles were functionalized with single-stranded DNA molecules and further hybridized with DNA modified with different fluorophores. By correlating the denaturation profiles of the DNA with the local temperature, temperature gradients for the vicinity of the excited nanoparticles were determined.
Assuntos
DNA/química , Hipertermia Induzida/métodos , Magnetismo , NanopartículasRESUMO
Lipospheres made from soy bean oil and a combination of the cationic lipid Metafectene and the helper lipid dioleoylphosphatidyl-ethanolamine were functionalized with magnetic nanoparticles (NPs) and small interfering RNA (siRNA). The resulting magnetic lipospheres loaded with siRNA are proven here as efficient nonviral vectors for gene silencing. Embedding magnetic NPs in the shell of lipospheres allows for magnetic force-assisted transfection (magnetofection) as well as magnetic targeting in both static and fluidic conditions mimicking the bloodstream.