ABSTRACT
Although low-cost nanozymes with excellent stability have demonstrated the potential to be highly beneficial for nanocatalytic therapy (NCT), their unsatisfactory catalytic activity accompanied by intricate tumor microenvironment (TME) significantly hinders the therapeutic effect of NCT. Herein, for the first time, a heterojunction (HJ)-fabricated sonoresponsive and NIR-II-photoresponsive nanozyme is reported by assembling carbon dots (CDs) onto TiCN nanosheets. The narrow bandgap and mixed valences of Ti3+ and Ti4+ endow TiCN with the capability to generate reactive oxygen species (ROS) when exposed to ultrasound (US), as well as the dual enzyme-like activities of peroxidase and glutathione peroxidase. Moreover, the catalytic activities and sonodynamic properties of the TiCN nanosheets are boosted by the formation of HJs owing to the increased speed of carrier transfer and the enhanced electron-hole separation. More importantly, the introduction of CDs with excellent NIR-II photothermal properties could achieve mild hyperthermia (43 °C) and thereby further improve the NCT and sonodynamic therapy (SDT) performances of CD/TiCN. The synergetic therapeutic efficacy of CD/TiCN through mild hyperthermia-amplified NCT and SDT could realize "three-in-one" multimodal oncotherapy to completely eliminate tumors without recurrence. This study opens a new avenue for exploring sonoresponsive and NIR-II-photoresponsive nanozymes for efficient tumor therapy based on semiconductor HJs.
Subject(s)
Hyperthermia, Induced , Neoplasms , Humans , Carbon , Pain Management , Peroxidase , Peroxidases , Neoplasms/drug therapy , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Nanozymes have shown promising potential in disease treatment owing to the advantages of low-cost, facile fabrication, and high stability. However, the highly complex tumor microenvironment (TME) and inherent low catalytic activity severely restrict the clinical applications of nanozymes. Herein, a novel mild hyperthermia-enhanced nanocatalytic therapy platform based on Z-scheme heterojunction nanozymes by depositing N-doped carbon dots (CDs) onto Nb2 C nanosheets is constructed. CD@Nb2 C nanozymes not only display outstanding photothermal effects in the safe and efficient NIR-II window but also possess triple enzyme-mimic activities to obtain amplified ROS levels. The triple enzyme-mimic activities and NIR-II photothermal properties of CD nanozymes are enhanced by the construction of Z-scheme heterojunctions owing to the accelerated carrier transfer process. More importantly, the introduction of mild hyperthermia can further improve the peroxidase-mimic and catalase-mimic activities as well as the glGSH depletion abilities of CD@Nb2 C nanozymes, thereby producing more ROS to efficiently inhibit tumor growth. The combined therapy effect of CD@Nb2 C nanozymes through mild NIR-II photothermal-enhanced nanocatalytic therapy can achieve complete tumor eradication. This work highlights the efficient tumor therapy potential of heterojunction nanozymes.
Subject(s)
Carbon , Neoplasms , Humans , Reactive Oxygen Species , Cell Line, Tumor , Neoplasms/drug therapy , Phototherapy , Tumor MicroenvironmentABSTRACT
Metal-free layered black phosphorus (BP) nanosheets with an excellent photothermal effect and large surface areas have been widely applied in biomedicine but are easily oxidized in ambient conditions yielding insulating phosphorus oxides adsorbed on its surface. Several chemical-functionalized strategies have been explored to protect thin layers of BP; however, the performance of passivated BP often decreases significantly, falling behind the single BP due to the strong structure perturbation. Herein, we designed and constructed 0D/2D hybrid photothermal agents by assembling NIR-II-responsive carbon dots (NIR-II-CDs) on BP nanosheets. NIR-II-CDs improve the ambient stability of BP by isolating them from water and oxygen and enhance the photothermal properties of BP nanosheets. Such NIR-II-CD/BP hybrids strengthen the light-harvesting ability, achieving high photothermal conversion efficiencies in the NIR-I (77.3%) and NIR-II (61.4%) windows, which is significantly higher than that of pristine BP (49.5 and 28.4% at 808 and 1064 nm). Owing to the intrinsic advantage of 1064 nm laser and the excellent PTT effect of our NIR-II-CD/BP hybrids, complete tumor eradication was realized in a deep-tissue tumor model.
Subject(s)
Carbon/chemistry , Nanostructures/chemistry , Neoplasms/drug therapy , Phosphorus/chemistry , Photochemotherapy/methods , Animals , Cell Line, Tumor , Humans , Infrared Rays , Lasers , Mice , Photochemotherapy/instrumentation , Quantum Dots/chemistryABSTRACT
Currently, one of the major hurdles hindering the clinical applications of photothermal therapy (PTT) and photothermal-chemo combination therapy (PCT) is the lack of highly efficient, readily derived, and irradiation-safe photothermal agents in the biologically transparent window. Herein, we report the first design and rational construction of 0D/2D/0D sandwich heterojunctions for greatly enhanced PTT and PCT performances using 0D N-doped carbon dots and 2D MoS2 nanosheets as the assembly units. The well-matching heterojunctions enabled an additional enhancement in NIR absorbance owing to the carrier injection from carbon dots to MoS2 nanosheets, and achieved a much higher photothermal conversion efficiency (78.2%) than that of single NIR-CDs (37.6%) and MoS2 (38.3%) only. In virtue of the heterojunction-based PTT, complete tumor recession without recurrence or pulmonary metastasis was realized at an ultralow and safe laser exposure (0.2 W cm-2) below the skin tolerance irradiation threshold. Furthermore, by taking advantage of the strong X-ray attenuation and effective drug loading capacity of MoS2 nanosheets, the CT imaging-guided PCT was achieved at 0.1 W cm-2, without inducing noticeable toxic side effects. Our findings can substantiate the potential of a novel 0D/2D heterojunction for cancer theranostics.