RESUMO
Heterogeneity of cancer cells and drug resistance require multiple therapeutic approaches for comprehensive treatment. In this study, temperature-sensitive liposomes containing anti-cancer agent tanespimycin (17-AAG) and photosensitizer IR 820 were developed for combination of phototherapy and chemotherapy. The temperature-sensitive liposomes composed of DPPC, cholesterol, DSPE-PEG, 17-AAG, and IR 820 (LP-AI) at weight ratio of 35/15/3/2/2 were formulated as a thin film using extrusion and evaluated for particle size, morphology and drug release profile. Furthermore, the anticancer effect of combined therapy was examined in vitro and in vivo in SCC-7 and MCF-7 cell lines. As a result, LP-AI was prepared at particle size of 166.7±1.3nm, PDI of 0.153±0.012, and ζ-potential of -32.6±0.8mV. After NIR irradiation (660 and 808nm laser), LP-AI could generate heat and ROS and enhance drug release from nanoparticles which were useful to kill the cancer cells. These were confirmed by in vitro cytotoxicity as well as in vivo effective ablation of tumors. In conclusion, fast drug release and enhanced treatment efficacy of LP-AI indicate the potential of integrating photo- and chemotherapy for synergistic anti-cancer effects.
Assuntos
Antineoplásicos/farmacologia , Benzoquinonas/farmacologia , Lactamas Macrocíclicas/farmacologia , Lipossomos/química , Fotoquimioterapia , Temperatura , Linhagem Celular Tumoral , HumanosRESUMO
In 2014, an outbreak of Ebola virus spread rapidly in West Africa. The epidemic killed more than 10,000 people and resulted in transmissions outside the endemic countries. WHO hopes for effective vaccines by the end of 2015. Numerous vaccine candidates have been proposed, and several are currently being evaluated in humans. Among the vaccine candidates are vectors derived from adenovirus (Ad). Despite previous encouraging preclinical and Phase I/II trials, Ad vectors used in three Phase II trials targeting HIV were prematurely interrupted because of the lack of demonstrated efficacy. The vaccine was not only ineffective but also led to a higher rate of HIV acquisition. In this context, the authors discuss the potential benefits, risks and impact of using Ad-derived vaccines to control Ebola virus disease.