RESUMEN
Exploring a combined phototherapeutic strategy to overcome the limitations of a single mode therapy and inducing high anticancer efficiency is highly promising for precision cancer nanomedicine. However, a single-wavelength laser activates dual photothermal/photodynamic therapy (PTT/PDT) treatment is still a formidable challenge. Herein, we strategically design and fabricate a multifunctional theranostic nanosystem based on chlorin e6-functionalized polydopamine (PDA) coated prussian blue/manganese dioxide nanoparticles (PB-MnO2@PDA-Ce6 NPs). Interestingly, the obtained PB-MnO2@PDA NPs not only offer an effective delivery system for Ce6 but also provide strong optical absorption in the near-infrared range, endowing high antitumor efficacy of PTT. More importantly, the as-prepared PB-MnO2@PDA-Ce6 nanoagents exhibit an effective oxygen generation, superior reactive oxygen species (ROS), and outstanding photothermal conversion ability to greatly improve PTT and PDT treatments. As a result, both in vitro and in vivo treatments guided by MR imaging on liver cancer cells reveal the complete cell/tumor eradication under a single wavelength of 660 nm laser irradiation, implying the simultaneous synergistic PDT/PTT effects triggered by PB-MnO2@PDA-Ce6 nanoplatform, which are much higher than individual treatment. Taken together, our phototherapeutic nanoagents exhibit an excellent therapeutic performance, which may act as a nanoplatform to find safe and clinically translatable routes to accelerate cancer therapeutics.
Asunto(s)
Ferrocianuros/química , Indoles/química , Rayos Infrarrojos , Compuestos de Manganeso/química , Nanopartículas/química , Óxidos/química , Oxígeno/metabolismo , Fotoquimioterapia/métodos , Polímeros/química , Línea Celular Tumoral , Diseño de Fármacos , Humanos , Indoles/farmacología , Rayos Láser , Polímeros/farmacologíaRESUMEN
Exploration of versatile nanoplatforms within one single nanostructure for multidisciplinary treatment modalities, especially achieving a synergistic therapeutic efficacy of combinational gene/photothermal cancer therapy is still a great challenge in biomedicine and nanotechnology. In this study, a unique photothermal nanocarrier has successfully been designed and developed for a combination of gene therapy (GT) and photothermal therapy (PTT) of cancer cells. Surface-engineered iron oxides (α-Fe2O3) nanoparticles (NPs) with poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings are synthesized using a one-pot in situ oxidative polymerization method. The results show that the as-prepared α-Fe2O3@PEDOT core-shell NPs with a uniform particle size exhibit positively charged surfaces, facilitating efficient siRNA Bcl-2 (B-cell lymphoma-2) uptake for delivery to breast cancer cells. More importantly, α-Fe2O3@PEDOT core-shell NPs not only display good biocompatibility and water dispersibility but also strong optical absorption enhancement in the Vis-NIR region as compared to α-Fe2O3 NPs. The obtained α-Fe2O3@PEDOT core-shell NPs show an efficient photothermal conversion efficacy (η = 54.3%) and photostability under NIR laser irradiation. As a result, both in vitro and in vivo biological studies on two types of breast cancer cells/tumors treated with α-Fe2O3@PEDOT-siRNA nanocomplexes demonstrate high cancer cell apoptosis and tumor inhibition induced by synergistic GT/PTT therapy under mild conditions compared to an individual GT or PTT alone. Taken together, this is the first example of the use of an α-Fe2O3@PEDOT core-shell nanoagent as a siRNA delivery nanocarrier for highly effective gene/photothermal combination anticancer therapy.