RESUMO
High intensity focused ultrasound (HIFU) is a noninvasive thermal ablation technique for the treatment of benign and malignant solid masses. To improve the efficacy of HIFU ablation, we developed poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating perfluoropentane (PFP) and hematoporphyrin monomethyl ether (HMME) as synergistic agents (HMME+PFP/PLGA). Two-step biotin-avidin pre-targeting technique was applied for the HIFU ablation. We further modified the nanoparticles with streptavidin (HMME+PFP/PLGA-SA). HMME+PFP/PLGA-SA were highly dispersed with spherical morphology (477.8 ± 81.8 nm in diameter). The encapsulation efficiency of HMME and PFP were 46.6 ± 3.3% and 40.1 ± 2.6%, respectively. The binding efficiency of nanoparticles to streptavidin was 95.5 ± 2.5%. The targeting ability of the HMME+PFP/PLGA-SA nanoparticles was tested by parallel plate flow chamber in vitro. In the pre-targeting group (HMME+PFP/PLGA-SA), a large number of nanoparticles bound to the peripheral and surface of the cell. In the HIFU ablation experiment in vivo, compared with the other groups, the largest gray-scale changes and coagulation necrosis areas were observed in the pre-targeting (HMME+PFP/PLGA-SA) group, with the lowest energy efficiency factor value. Moreover, the microvessel density and proliferation index declined, while the apoptotic index increased, in the tumor tissue surrounding the coagulation necrosis area in the pre-targeting group. Meanwhile, the survival time of the tumor-bearing nude mice in the pre-targeting group was significantly longer than that in the HIFU treatment group. These results suggest that HMME+PFP/PLGA-SA have high potential to act as synergistic agents in HIFU ablation.
Assuntos
Anticorpos Monoclonais/farmacologia , Neoplasias da Mama/terapia , Fluorocarbonos/química , Hematoporfirinas/química , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Nanopartículas/administração & dosagem , Animais , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Terapia Combinada , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Células Tumorais Cultivadas , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
By using line transect method, the distribution patterns of giant panda population and its sympatric companion wildlife species in Foping and Guanyinshan nature reserves were investigated in October 2007 and April 2008, and the environmental factors affecting the spatial distribution of giant panda activity were analyzed. The giant panda population and its sympatric companion wildlife species in the two reserves had the similar distribution patterns, and the density and distribution range of giant panda were smaller in Guanyinshan than in Foping. Giant panda had two high-density distribution areas in Foping, but no activity trace in most parts of Guanyinshan. The activity trace of Budorcas taxicolor, Naemorhedus goral and Sus scrofa was more in Guanyinshan than in Foping. Anthropogenic interference might affect the distribution pattern of giant panda.
