RESUMEN
Although phototherapy has been considered as an emerging and promising technology for cancer therapy, its therapeutic specificity and efficacy are severely limited by nonspecific uptake by normal tissues, tumor hypoxia, and so on. Herein, combination-responsive strategy (CRS) is applied to develop one kind of hyaluronic acid-hybridized Ru nanoaggregates (HA-Ru NAs) for enhanced cancer phototherapy via the reasonable integration of receptor-mediated targeting (RMT) and tumor-microenvironment responsiveness (TMR). In this nanosystem, the HA component endows HA-Ru NAs with RMT characteristic to selectively recognize CD44-overexpressing cancer cells, whereas the Ru nanocomponent makes HA-Ru NAs have TMR therapy activity. Specially, the Ru nanocomponent not only has near-infrared-mediated photothermal and photodynamic functions but also can catalyze H2O2 in tumor tissue to produce O2 for the alleviation of tumor hypoxia and toxic â¢OH for chemodynamic therapy. Benefitting from these, HA-Ru NAs can be considered as a promising kind of CRS nanoplatforms for synergistic photothermal/photodynamic/chemodynamic therapies of cancer, which will not only effectively improve the phototherapeutic specificity and efficacy but also simplify the therapeutic nanosystems. Meanwhile, HA-Ru NAs can serve as a photoacoustic and computed tomography imaging contrast agent to monitor tumors. Such CRS nanoplatforms hold significant potential in improving therapeutic specificity and efficacy for enhanced cancer phototheranostics.
Asunto(s)
Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , Nanomedicina Teranóstica , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Medios de Contraste/química , Medios de Contraste/farmacología , Doxorrubicina/química , Humanos , Ácido Hialurónico/química , Ratones , Nanopartículas/administración & dosificación , Nanopartículas/química , Neoplasias/patología , Fotoquimioterapia , Rutenio/química , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
It is of extreme importance to reduce side effects resulting from the nonspecific uptake of phototherapeutic agents by normal tissues. Currently, the single responsive strategy still cannot entirely satisfy the requirements of practical applications. In this study, we developed one kind of combination-responsive phototherapeutic nanoplatforms, where oxygen-deficient molybdenum oxide (MoO3- x) hybridized hyaluronic acid (HA) hollow nanospheres, namely, MoO3- x@HA HNSs, were constructed via a facile one-step method. In MoO3- x@HA HNSs, the reasonable combination of actively targeted specificity endowed by the HA component and tumor microenvironment-responsive phototherapy activity induced by the MoO3- x component can effectively improve the precision of phototherapy. The in vitro and in vivo experimental results confirm that MoO3- x@HA HNSs can selectively kill CD44-overexpressing cancer cells and inhibit tumor growth under an 808 nm laser irradiation, revealing their remarkable synergistic photothermal therapy/photodynamic therapy effect with CD44 receptor-targeted specificity and pH responsiveness in treating cancer. We also prove that MoO3- x@HA HNSs can serve as one kind of contrast agent to achieve the computed tomography/photoacoustic imaging. Encouraged by these results, it is anticipated that the reasonable combination of active targeting and tumor microenvironment responsiveness can be a promising strategy to develop phototherapeutic nanoplatforms for precise multimodality cancer theranostics.