RESUMEN
There are tricky challenges in tumor therapy due to the hypoxic tumor microenvironment, inevitably inhibiting the treatment efficacy of the traditional photodynamic therapy (PDT), radiation therapy (RT), and sonodynamic therapy (SDT). Herein, to overcome tumor hypoxia limitation, we constructed a near-infrared II (NIR-II) light-triggered thermodynamic therapy (TDT) nanoplatform of Au@mSiO2-AIPH@PCM/PEG (ASAPP) by integrating the Au nanorods (Au NRs) and thermally activated alkyl free radical-releasing molecules (AIPH). Au NRs@mSiO2 was used as a photothermally responsive material and AIPH carrier, and the hot-melt phase-change material (PCM) was used as a capping agent to prevent leakage of AIPH during blood circulation. Upon NIR-II light irradiation, heat-triggered free radical release from AIPH was successfully achieved for killing cancer cells in vitro and in vivo without oxygen dependence, leading to synergistically enhanced antitumor therapy.
Asunto(s)
Hipertermia Inducida , Nanotubos , Neoplasias , Fotoquimioterapia , Humanos , Terapia Fototérmica , Oro/química , Neoplasias/terapia , Neoplasias/patología , Radicales Libres , Nanotubos/química , Termodinámica , Microambiente TumoralRESUMEN
Excessive production of hydrogen sulfide (H2 S) plays a crucial role in the progress of colon cancer. Construction of tumor-specific H2 S-activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2 S triggered Co-doped polyoxometalate (POM-Co) cluster with self-adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2 S/glutathione (GSH) is designed for synergistic enhanced tumor-specific photothermal and chemodynamic therapy. The designed POM-Co nanocluster holds H2 S responsive "turn-on" photothermal property in colon cancer via self-assembling to form large-sized POM-CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM-CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)-catalyzed â¢OH production and Russell mechanism-enabled 1 O2 generation with GSH consumption, respectively. More importantly, the degraded POM-CoS is reactivated by endogenous H2 S for recyclable and sustainable consumption of H2 S and GSH, resulting in tumor-specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment-driven nanoprobes with controllable biodegradation for precise and sustainable anti-tumor therapy.