RESUMO
There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy.
Assuntos
Ouro/administração & dosagem , Hipertermia Induzida/métodos , Nanoconchas , Fototerapia/métodos , Neoplasias de Mama Triplo Negativas/terapia , Animais , Linhagem Celular Tumoral , Feminino , Ouro/química , Humanos , Hipertermia Induzida/instrumentação , Injeções Intravenosas , Lasers Semicondutores , Camundongos , Camundongos Nus , Nanomedicina/métodos , Tamanho da Partícula , Fototerapia/instrumentação , Polietilenoglicóis/química , Dióxido de Silício/química , Propriedades de Superfície , Fatores de Tempo , Transdutores , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Au nanoparticles with plasmon resonances in the near-infrared (NIR) region of the spectrum efficiently convert light into heat, a property useful for the photothermal ablation of cancerous tumors subsequent to nanoparticle uptake at the tumor site. A critical aspect of this process is nanoparticle size, which influences both tumor uptake and photothermal efficiency. Here, we report a direct comparative study of â¼90 nm diameter Au nanomatryoshkas (Au/SiO2/Au) and â¼150 nm diameter Au nanoshells for photothermal therapeutic efficacy in highly aggressive triple negative breast cancer (TNBC) tumors in mice. Au nanomatryoshkas are strong light absorbers with 77% absorption efficiency, while the nanoshells are weaker absorbers with only 15% absorption efficiency. After an intravenous injection of Au nanomatryoshkas followed by a single NIR laser dose of 2 W/cm(2) for 5 min, 83% of the TNBC tumor-bearing mice appeared healthy and tumor free >60 days later, while only 33% of mice treated with nanoshells survived the same period. The smaller size and larger absorption cross section of Au nanomatryoshkas combine to make this nanoparticle more effective than Au nanoshells for photothermal cancer therapy.
Assuntos
Ouro/química , Neoplasias Mamárias Experimentais/terapia , Nanopartículas Metálicas/química , Nanotecnologia/métodos , Neoplasias/terapia , Fotoquímica , Animais , Feminino , Humanos , Lasers , Teste de Materiais , Camundongos , Camundongos Nus , Nanoconchas , Transplante de Neoplasias , Óptica e Fotônica , Tamanho da Partícula , Polietilenoglicóis/química , Dióxido de Silício/químicaRESUMO
Microfluidic jetting is a promising method to produce giant unilamellar phospholipid vesicles for mimicking living cells in biomedical studies. We have investigated the chemical composition of membranes of vesicles prepared using this approach by means of Raman scattering spectroscopy. The membranes of all jetted vesicles are found to contain residuals of the organic solvent decane used in the preparation of the initial planar membrane. The decane inclusions are randomly distributed over the vesicle surface area and vary in thickness from a few to several tens of nanometers. Our findings point out that the membrane properties of jetted vesicles may differ considerably from those of vesicles prepared by other methods and from those of living cells.