RESUMO
A greener approach for the design of surface plasmon resonant gold nanoparticles has been obtained with a hydrosoluble fraction of an endemic asteraceae medicinal plant. This medicinal plant is originated from Indian Ocean and demonstrates its bioreducing activity in the design of stable green nanomedicine in aqueous media. This article describes the preclinical assessment of the efficacy of these novel nanocandidates on murine model by intratumoral and intravenous injections. It definitely demonstrates two key points in the treatment of cancer: 1) optimization of the tumor microenvironment targeting by specific ligands for a limited damage on healthy tissue, 2) the need to screen the specific irradiation dose (time, power) taking into account the type of tumor.
Assuntos
Ouro/química , Química Verde/métodos , Nanopartículas Metálicas/química , Ressonância de Plasmônio de Superfície/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Asteraceae/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ouro/administração & dosagem , Ouro/farmacocinética , Humanos , Injeções Intralesionais , Injeções Intravenosas , Luz , Nanopartículas Metálicas/administração & dosagem , Camundongos , Nanomedicina/métodos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Fototerapia/métodos , Estudo de Prova de Conceito , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiaçãoRESUMO
One of the most effective strategies to enhance the bioavailability and the therapeutic effect of hydrophobic drugs is the use of nanocarriers. We have used κ-carrageenan extracted from Kappaphycus alvarezii to produce oligocarrageenan via an enzymatic degradation process. Polycaprolactone (PCL) chains were grafted onto the oligocarrageenans using a protection/deprotection technique yielding polycaprolactone-grafted oligocarrageenan. The resulting amphiphilic copolymers formed spherical nanomicelles with a mean size of 187 ± 21 nm. Hydrophobic drugs such as curcumin were efficiently encapsulated in the micelles and released within 24-72 h in solution. The micelles were non-cytotoxic and facilitated the uptake of curcumin by endothelial EA-hy926 cells. They also increased the anti-inflammatory effect of curcumin in TNF-alpha-induced inflammation experiments. Finally, in vivo experiments supported a lack of toxicity in zebrafish and thus the potential use of polycaprolactone-grafted oligocarrageenan to improve the delivery of hydrophobic compounds to different organs, including liver, lung and brain as shown in mice.
