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1.
ACS Nano ; 13(12): 13965-13984, 2019 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-31730327

RESUMEN

Multidrug-resistant (MDR) bacterial infections are a severe threat to public health owing to their high risk of fatality. Noticeably, the premature degradation and undeveloped imaging ability of antibiotics still remain challenging. Herein, a selenium nanosystem in response to a bacteria-infected microenvironment is proposed as an antibiotic substitute to detect and inhibit methicillin-resistant Staphylococcus aureus (MRSA) with a combined strategy. Using natural red blood cell membrane (RBCM) and bacteria-responsive gelatin nanoparticles (GNPs), the Ru-Se@GNP-RBCM nanosystem was constructed for effective delivery of Ru-complex-modified selenium nanoparticles (Ru-Se NPs). Taking advantage of natural RBCM, the immune system clearance was reduced and exotoxins were neutralized efficiently. GNPs could be degraded by gelatinase in pathogen-infected areas in situ; therefore, Ru-Se NPs were released to destroy the bacteria cells. Ru-Se NPs with intense fluorescence imaging capability could accurately monitor the infection treatment process. Moreover, excellent in vivo bacteria elimination and a facilitated wound healing process were confirmed by two kinds of MRSA-infected mice models. Overall, the above advantages proved that the prepared nanosystem is a promising antibiotic alternative to combat the ever-threatening multidrug-resistant bacteria.


Asunto(s)
Biomimética , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Nanopartículas/química , Selenio/farmacología , Animales , Antibacterianos/farmacología , Infecciones Bacterianas , Materiales Biocompatibles/farmacología , Bovinos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/ultraestructura , Fluorescencia , Gelatina/química , Evasión Inmune/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/ultraestructura , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Nanopartículas/ultraestructura , Especies Reactivas de Oxígeno/metabolismo
2.
Nanoscale ; 11(39): 18209-18223, 2019 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-31560010

RESUMEN

Rheumatoid arthritis (RA) is a degenerative joint disease caused by autoimmunity; for the effective treatment of RA while avoiding the side effects of conventional drugs, we have proposed a new therapeutic strategy to eliminate the inflammatory response in RA by regulating the immune system that promotes the transformation of M1-type macrophages to M2-type macrophages. Herein, we designed and synthesized a core-shell nanocomposite (QRu-PLGA-RES-DS NPs), which showed an effective therapeutic effect on RA by accurately inducing the polarization of M2 macrophages. In this system, the quadrilateral ruthenium nanoparticles (QRuNPs) with a photothermal effect were utilized as a core and the thermosensitive molecular poly (lactic-co-glycolic acid) (PLGA) modified with the targeted molecule dextran sulfate (DS) was employed as a shell. Then, the nanocarrier QRu-PLGA-DS NPs effectively improved the water solubility and targeting of resveratrol (RES) through self-assembly. Therefore, the QRu-PLGA-RES-DS NPs significantly enhanced the ability of RES to reverse the M1 type macrophages to the M2 type macrophages through an accurate release. In vivo experiments further demonstrated that the QRu-PLGA-RES-DS NPs could effectively accumulate in the lesion area with an exogenous stimulus, and this significantly enhanced the transformation of the M2 type macrophages and decreased the recruitment of the M1 type macrophages. Furthermore, the QRu-PLGA-RES-DS NPs effectively treated RA by eliminating the inflammatory response; in addition, photoacoustic imaging (PA) of the QRu NPs provided image guidance for the distribution and analysis of nanomedicine in inflammatory tissues. Hence, this therapeutic strategy promotes the biological applications of Ru-based nanoparticles in disease treatment.


Asunto(s)
Hipertermia Inducida , Macrófagos/metabolismo , Nanocompuestos , Fototerapia , Resveratrol , Fiebre Reumática/terapia , Animales , Células Endoteliales de la Vena Umbilical Humana , Humanos , Macrófagos/patología , Ratones , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacología , Células RAW 264.7 , Resveratrol/farmacocinética , Resveratrol/farmacología , Fiebre Reumática/metabolismo , Fiebre Reumática/patología , Rutenio/química , Rutenio/farmacocinética , Rutenio/farmacología
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