Eight-arm polyethylene glycol nanoconjugates for brain targeted delivery of photosensitizer / 中国药科大学学报

@#The aim of this study was to prepare the nanoconjugates for targeted photodynamic therapy of brain cancer by using eight-arm polyethylene glycol(8PEG)as the carrier and cRGD as the targeting ligand, and to investigate the antitumor effect and its mechanism. UV-Vis spectra and confocal microscopy were used for characterization and cellular uptake behavior of nanoconjugates respectively. Alamar Blue assay and Calcein AM/PI staining were applied to investigate the cytotoxocity of nanoconjugates against tumor cells, and tumor spheroid growth curve was used to assess the tumor growth suppression effect. In addition, the generation of reactive oxygen species(ROS), apoptosis and spheroid permeability test was used to reveal the antitumor mechanism of nanoconjugates. The results showed that cRGD-8PEG-IR700 was taken up efficiently by integrin overexpressed U87MG cells, while almost no uptake was found in integrin free NIH/3T3 cells. Remarkable photokilling effect against U87MG cells was only shown in cRGD-8PEG-IR700 group due to the light-induced ROS generation and apoptosis, whereas growth suppression effect was also observed in U87MG spheroids treated with cRGD-8PEG-IR700 plus light owing to the superior penetration ability of targeted nanoconjugates. Hence, tumor-targeted PEG nanoconjugates may provide a promising drug delivery system for photodynamic therapy of cancers.

Péptidos antimicrobianos: potencialidades terapéuticas / Antimicrobial peptides: their therapeutic potential

El aumento en la incidencia de las enfermedades infecciosas en los últimos años se ha favorecido por diferentes causas. Entre estas se destacan las inmunodeficiencias adquiridas (sida, trasplantes de órganos, quimioterapia oncológica), la migración de personas que trae consigo la posibilidad de importar enfermedades hacia poblaciones susceptibles, así como el excesivo empleo de antibióticos. Debido a esta situación se ha incrementado la búsqueda de nuevos candidatos terapéuticos para el desarrollo de terapias más efectivas. En este sentido los péptidos antimicrobianos constituyen una opción promisoria, pues presentan un amplio espectro de actividad frente a varios microorganismos patógenos. Además, se encuentran ampliamente distribuidos en la naturaleza, desde organismos unicelulares hasta mamíferos. Algunos péptidos antimicrobianos ya están siendo evaluados en estudios clínicos aunque muchos de ellos no han tenido resultados favorables in vivo debido a su poca estabilidad metabólica y toxicidad, entre otros. Con el fin de optimizar estas propiedades de los péptidos antimicrobianos se han trazado diferentes estrategias como la modificación química de su estructura y la conjugación con nanopartículas magnéticas. Es por eso que este artículo tiene el objetivo de revisar las potenciales aplicaciones terapéuticas de estas moléculas, teniendo en cuenta la información publicada al respecto en MedLine, Web of Science y Scopus en los últimos años

The growing incidence of infectious disease in recent years may be attributed to several causes, among them acquired immunodeficiencies (AIDS, organ transplant, oncological chemotherapy), human migration and the consequent import of diseases into susceptible populations, and the excessive use of antibiotics. This situation has fostered the search for new therapeutic candidates for the development of more effective treatments. Antimicrobial peptides are a promising alternative in this respect, due to their broad spectrum of activity against several pathogenic microorganisms. Moreover, they are widely distributed in nature, from unicellular organisms to mammals. Some antimicrobial peptides are already being evaluated in clinical studies, though many of them have not produced any favorable results in vivo due to their low metabolic stability and their toxicity, among other factors. Several strategies have been developed to overcome the above mentioned drawbacks, among them conjugation of microbial peptides with magnetic nanoparticles and chemical modification of their structure. The present study is aimed at reviewing the potential therapeutic applications of these molecules based on information published in MedLine, the Web of Science and Scopus in recent years.

Anticancer effects of heparinized mesoporous silicon nanoparticles drug carrier system on H22 tumor-bearing mice and its liver and kidney toxicity / 中国药理学与毒理学杂志

OBJECTIVE To investigate the antitumor effect and toxicity of doxorubicin-heparinized mesoporous silicon nanoparticles drug carrier system (DOX-HMSN) on H22 hepatoma mice. METHODS An experimental animal model of H22 hepatoma mice was established. Fifty male Kunming mice were divided into five groups:model control group,HMSN 8 mg?kg-1 group,DOX-HMSN 4,8 mg?kg-1 groups, and DOX 2 mg?kg-1(once every other day)group. Continuous intravenous injection was given once a day for 14 d. Tumor was completely stripped and weighed,and tumor inhibitory rate was determined. Pathological change of tumor tissue was observed by HE staining in H22 mice. White blood cell count was performed and the thymus index and spleen index were calculated. Levels of serum creatinine (Scr),blood urea nitrogen(BUN),glutamic pyruvic transaminase(GPT)and glutamic-oxalacetic transaminase(GOT)in serum were determined. BCL-2,BAX and vascular endothelial growth factor (VEGF)expression of tumor tissue were analyzed using Western blot. RESULTS The inhibitory rate of tumor was 20.5%,40.4%,54.8%,and 67.5%,respectively,in HMSN 8 mg?kg-1 group,DOX-HMSN 4, 8 mg?kg-1 group and DOX 2 mg?kg-1 group(P<0.01). HE results showed that HMSN 8 mg?kg-1,DOX-HMSN 4,8 mg?kg-1and DOX 2 mg?kg-1 induced tumor necrosis and nuclear dissolution of the tumor cells in H22 mice. The white blood cell count,thymus index and spleen index of mice were not signifi?cantly different between control group and HMSN group or DOX-HMSN 4 and 8 mg?kg-1 group. The levels of Scr and BUN of mice did not change obviously in HMSN 8 mg?kg-1or DOX-HMSN 4,8 mg?kg-1 groups. Compared with the model control group,the level of GPT and GOT of mice increased in the DOX 2 mg?kg-1group but decreased in HMSN 8 mg?kg-1 and DOX-HMSN 4 and 8 mg?kg-1 group(P<0.05). Compared with the control,the BAX/BCL-2 ratio(from 0.49 ± 0.06 to 0.79 ± 0.08,1.23 ± 0.14 and 1.04±0.14)increased but the VEGF expression of tumor(from 1.39±0.14 to 1.13±0.12,0.75±0.08 and 0.94 ± 0.09)decreased significantly in DOX-HMSN 4,8 mg?kg-1 and DOX 2 mg?kg-1 group(P<0.05). CONCLUSION DOX-HMSN can inhibit the tumor growth of H22 tumor-bearing mice and its antitumor mechanism might be related to inducing tumor cell necrosis and apoptosis and inhibiting tumor angiogenesis.