RESUMO
Silver sulfide nanoparticles (Ag2S-NP) hold promise for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA), and photothermal therapy (PTT). However, their NIR absorbance is relatively low, and previous formulations are synthesized using toxic precursors under harsh conditions and are not effectively cleared due to their large size. Herein, sub-5 nm Ag2S-NP are synthesized and encapsulated in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses are conducted using biocompatible, aqueous reagents under ambient conditions. The encapsulation of Ag2S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and PTT effects. AgPCPP nanoparticles exhibit potent contrast properties suitable for PA and NIRF imaging, as well as for computed tomography (CT). Furthermore, AgPCPP nanoparticles readily improve the conspicuity of breast tumors in vivo. Under NIR laser irradiation, AgPCPP nanoparticles significantly reduce breast tumor growth, leading to prolonged survival compared to free Ag2S-NP. Over time, AgPCPP retention in tissues gradually decreases, without any signs of acute toxicity, providing strong evidence of their safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion after fulfilling diagnostic and therapeutic tasks, offering good prospects for clinical translation.
Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/terapia , Fototerapia/métodos , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodos , PolímerosRESUMO
Silver sulfide nanoparticles (Ag 2 S-NP) have been proposed for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA) and photothermal therapy (PTT). However, their absorbance is relatively low in the NIR window used in these applications, and previous formulations were synthesized using toxic precursors under harsh conditions and have clearance issues due to their large size. Herein, we synthesized sub-5 nm Ag 2 S-NP and encapsulated them in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses were conducted using biocompatible reagents in the aqueous phase and under ambient conditions. We found that the encapsulation of Ag 2 S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and photothermal heating effects. We therefore found that AgPCPP have potent contrast properties for PA and NIRF imaging, as well as for computed tomography (CT). We demonstrated the applicability of AgPCPP nanoparticles as a multimodal imaging probe that readily improves the conspicuity of breast tumors in vivo . PTT was performed using AgPCPP with NIR laser irradiation, which led to significant reduction in breast tumor growth and prolonged survival compared to free Ag 2 S-NP. Lastly, we observed a gradual decrease in AgPCPP retention in tissues over time with no signs of acute toxicity, thus providing strong evidence of safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion once the diagnostic and therapeutic tasks are fulfilled, thus providing good prospects for translation to clinical use.
RESUMO
Ultrasmall silver sulfide nanoparticles (Ag 2 S-NP) have been identified as promising contrast agents for a number of modalities and in particular for dual-energy mammography. These Ag 2 S-NP have demonstrated marked advantages over clinically available agents with the ability to generate higher contrast with high biocompatibility. However, current synthesis methods are low-throughput and highly time-intensive, limiting the possibility of large animal studies or eventual clinical use of this potential imaging agent. We herein report the use of a scalable silicon microfluidic system (SSMS) for the large-scale synthesis of Ag 2 S-NP. Using SSMS chips with 1 channel, 10 parallelized channels, and 256 parallelized channels, we determined that the Ag 2 S-NP produced were of similar quality as measured by core size, concentration, UV-visible spectrometry, and in vitro contrast generation. Moreover, by combining parallelized chips with increasing reagent concentration, we were able to increase output by an overall factor of 3,400. We also found that in vivo imaging contrast generation was consistent across synthesis methods and confirmed renal clearance of the ultrasmall nanoparticles. Finally, we found best-in-class clearance of the Ag 2 S-NP occurred within 24 hours. These studies have identified a promising method for the large-scale production of Ag 2 S-NP, paving the way for eventual clinical translation.
RESUMO
La alta morbimortalidad en aneurismas intracraneales exige la identificación rápida de los síntomas de alarma y el tratamiento oportuno en caso de ruptura. De ahí la importancia de las imágenes diagnósticas para identificar a los pacientes en riesgo y definir el manejo endovascular o quirúrgico. Revisamos los criterios para el uso del stent redireccionador de flujo en aneurismas intracraneales, método endovascular que reduce las comorbilidades, el tiempo quirúrgico y la estancia hospitalaria. Estudio descriptivo retrospectivo de 2010 a 2012 de siete casos. Se presentan las complicaciones siendo la cefalea y la trombosis posterior al procedimiento las más frecuentes. El tratamiento endovascular es seguro, eficaz e innovador y por tanto puede implementarse y difundirse.
High morbidity and mortality associated with intracranial aneurysms requires prompt recognition of alarm symptoms due to rupture and timely treatment. There fore, diagnostic imaging is very important to identify patients in risk andto define endovascular or surgical management. We reviewed the criteria for the uses of flow-diverting stents in intracranialaneurysms, an endovascular method which reduces comorbidities, surgical time and hospital stay. This isa descriptive retrospective trial of seven cases, conducted from 2010 to 2012. Complications were reviewed evidencingpost procedural headache and thrombosis as the commonest. Endovascular treatment is safe, efficient and innovative,thus, it may be implemented and diffused.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Aneurisma Intracraniano , Transtornos Cerebrovasculares , Morbidade , StentsRESUMO
La hepatitis A tiene una prevalencia o incidencia en los países en desarrollo de 50 a 100 por cada 100000 personas. La presentación atípica de la hepatitis A bifásica, es rara. El objetivo es presentar 9 casos de niños con hepatitis A bifásica. Se estudiaron nueve niños de edades comprendidas entre los 7 y 13 años (edad media 8,6 años); 5 varones con antecedentes de fiebre, vómito, ictericia, dolor abdominal y coluria de 3 a 5 días de evolución, e IgM para la hepatitis A (IgM VHA) positivo. Después de un mes de evolución asintomáticos, se volvieron a presentar iguales manifestaciones clínicas del primer episodio, con la presencia de IgM VHA positiva otra vez. La media de las pruebas de función hepática en el segundo cuadro fueron: ALT 1258 U/L,AST 986 U/l, bilirrubina directa 5,87 mg/dl, y fosfatasa alcalina 580 U/L. En ninguno se informó anomalías a la ecografía abdominal y la serología de hepatitis autoinmune fue negativa. No hubo morbilidad en los niños. La hepatitis agudaApuede tener entre un 3% a 20% de casos con más de un pico de aminotransferasas, que se eleva entre las 2 y 8 semanas después del primer cuadro. Las hipótesis para explicar ello, son fenómenos de reinfección y autoinmunes. En general, la evolución es satisfactoria.
Hepatitis A has a prevalence or incidence in developing countries from 50 to 100 per 100,000 people. The atypical presentation of biphasic hepatitis A, is rare. The objective was to report 9 cases of children with biphasic hepatitis A. We studied 9 children aged between 7 and 13 years (mean age 8.6 years), including 5 males with a history of fever, vomiting, jaundice, abdominal pain, and coluria for about 3 to 5 days of evolution, and IgM to hepatitisA(IgMVHA) positive. After a mean month evolution asymptomatic, again showed the same clinic manifestations for the second time in the presence of IgM VHA positive again. The median liver function tests in the second frame were ALT 1258 U/L, AST 986 U/L, direct bilirubin 5.87 mg/dL, FA 580 U/L. In all reported no abdominal ultrasound abnormalities and autoimmune hepatitis serology was negative. There was no morbidity in children. Acute hepatitisAcan take on 3%-20% of cases with more than 1 peak of aminotransferases, which can be raised between 2 and 8 weeks after the first frame. Hypotheses to explain this, are reinfection and autoimmune phenomena. In general, evolution is satisfactory.