RESUMEN
Rattle-structured nanoparticles with movable cores, porous shells and hollow interiors have shown great effectiveness in drug delivery and cancer theranostics. Targeting autophagy and glucose have provided alternative strategies for cancer intervention therapy. Herein, rattle-structured polydopamine@mesoporous silica nanoparticles were prepared for in vivo photoacoustic (PA) imaging and augmented low-temperature photothermal therapy (PTT) via complementary autophagy inhibition and glucose metabolism. Methods: The multifunctional rattle-structured nanoparticles were designed with the nanocore of PDA and the nanoshell of hollow mesoporous silica (PDA@hm) via a four-step process. PDA@hm was then loaded with autophagy inhibitor chloroquine (CQ) and conjugated with glucose consumer glucose oxidase (GOx) (PDA@hm@CQ@GOx), forming a corona-like structure nanoparticle. Results: The CQ and GOx were loaded into the cavity and decorated onto the surface of PDA@hm, respectively. The GOx-mediated tumor starvation strategy would directly suppress the expression of HSP70 and HSP90, resulting in an enhanced low-temperature PTT induced by PDA nanocore. In addition, autophagy inhibition by the released CQ made up for the loss of low-temperature PTT and starvation efficiencies by PTT- and starvation-activated autophagy, realizing augmented therapy efficacy. Furthermore, the PDA nanocore in the PDA@hm@CQ@GOx could be also used for PA imaging. Conclusion: Such a "drugs" loaded rattle-structured nanoparticle could be used for augmented low-temperature PTT through complementarily regulating glucose metabolism and inhibiting autophagy and in vivo photoacoustic imaging.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Portadores de Fármacos/química , Neoplasias/tratamiento farmacológico , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Cloroquina/administración & dosificación , Cloroquina/farmacocinética , Liberación de Fármacos , Femenino , Glucosa Oxidasa/administración & dosificación , Glucosa Oxidasa/farmacocinética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Hipotermia Inducida/métodos , Indoles/química , Ratones , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/patología , Terapia Fototérmica/métodos , Polímeros/química , Dióxido de Silicio/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Rattle-type porous carbon microcapsules (RPCMs) were deliberately designed to combine multiple functions with the aim of improving the applicability of amorphous carbon in a synergistic fashion. A movable Fe3O4 nanocluster coated with porous carbon is encapsulated in the cavity of a carbon microcapsule with an eggshell-like characteristic, allowing for storage, adsorption, and exchange of matters through the mesoporous channels of the carbon layer. The synthetic strategy of RPCMs is flexible and universal, involving the constitution and carbonization of Fe3O4@PF@PS@PF template particles. This results in a double carbon shell and a sandwiched hollow cavity with a movable magnetic core. There is evidence that RPCMs possess large surface areas, hierarchical pore sizes, hydrophobicity, and magnetic responsiveness. Hence, diverse applications have been investigated. It is proved that RPCMs exhibit excellent performance in the effective enrichment of peptides/proteins. The detection limit toward peptides could reach as low as 10 nM, and the enrichment capacity toward MYO protein is as high as 410 mg/g (protein/beads). Furthermore, RPCMs are able to harvest proteins in complex real samples such as fetal bovine serum and rabbit blood. In addition, RPCMs could be fabricated in a supercapacitor electrode and display outstanding energy-storage performance. The electrochemical measurements demonstrate that RPCM-based electrodes have a specific capacitance of as high as 216 F/g (0.1 A/g), long-term cycling stability with a capacitance retention of 92.4% over 1000 cycles (0.2 A/g), and good electronic conductivity.