RESUMO
Multifunctional nanoparticles have high potential as targeting delivery vehicles for cancer chemotherapy. In this study, silver-decorated gold nanorods (AuNR\Ag) have been successfully used to deliver specific, targeted chemotherapy against breast cancer (MCF7) and prostate carcinoma (PC3) cell lines. Doxorubicin, a commonly used chemotherapy, and anti-Epithelial cell adhesion molecule (anti-EpCAM) antibodies were covalently bonded to thiolated polyethylene glycol-coated AuNR\Ag, and the resultant system was used to deliver the drugs to cancer cells in vitro. Furthermore, these nanoparticles have a unique spectral signature by surface enhanced Raman spectroscopy (SERS), which enables reliable detection and monitoring of the distribution of these chemotherapy constructs inside cells. The development of interest in a plasmonic nano drugs system with unique spectroscopic signatures could result in a clinical approach to the precise targeting and visualization of cells and solid tumors while delivering molecules for the enhanced treatment of cancerous tumors.
Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Ouro/química , Nanotubos/química , Prata/química , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Doxorrubicina/farmacologia , Molécula de Adesão da Célula Epitelial/imunologia , Humanos , Terapia de Alvo Molecular , Análise Espectral RamanRESUMO
Sepsis triggers a complex series of pathophysiologic events involving inflammatory responses and coagulation abnormalities. While circulating blood platelets are well-characterized for their contributions to coagulation, increasingly platelet-dependent effects on inflammation are being recognized. Here, we focus on the platelet membrane receptor, glycoprotein VI (GPVI), and its role in platelet microparticle (pMP) release. The GPVI receptor is a platelet-specific collagen membrane receptor that, upon ligand binding, facilitates the release of pMPs. As membrane-bound platelet fragments of less than 1 µm, pMPs are known to have both pro-inflammatory and pro-coagulant properties. Thus, pMPs are potentially impacting sepsis at multiple stages of the inflammatory response. Studies are presented documenting the impact of the most common GPVI haplotypes, GPVIa and GPVIb, on pMP levels and release in healthy individuals (n = 49). The GPVIa haplotype corresponds to an approximately twofold increase in circulating pMPs as a percentage of total microparticles in healthy individuals along with a heightened in vitro release of pMPs. Additionally, patients admitted to a paediatric intensive care unit (ICU) (n = 73) with an initial diagnosis of sepsis were recruited and their GPVI haplotypes determined. Septic patients of the GPVIa haplotype (n = 59) were statistically more likely to present with a diagnosis of severe sepsis or septic shock, as compared with GPVIb individuals (n = 14). Independent disease classification via PELOD-2 and Pediatric Risk of Mortality III scores confirmed individuals with the GPVIa haplotype were more likely to have significant organ failure. Thus, GPVI haplotypes influence pMP levels in the circulation and are predictive of sepsis severity when presenting to the ICU.