Stimuli-Responsive Small-on-Large Nanoradiosensitizer for Enhanced Tumor Penetration and Radiotherapy Sensitization

Abstract

Development of an efficient nanoradiosensitization system that enhances the radiation doses in cancer cells to sensitize radiotherapy (RT) while sparing normal tissues is highly desirable. Here, we construct a tumor microenvironment (TME)-responsive disassembled small-on-large molybdenum disulfide/hafnium dioxide (MoS 2 /HfO 2 ) dextran (M/H-D) nanoradiosensitizer. The M/H-D can degrade and release the HfO 2 nanoparticles (NPs) in TME to enhance tumor penetration of the HfO 2 NPs upon near-infrared (NIR) exposure, which can solve the bottleneck of insufficient internalization of the HfO 2 NPs. Simultaneously, the NIR photothermal therapy increased peroxidase-like catalytic efficiency of the M/H-D nanoradiosensitizer in TME, which selectively catalyzed intratumorally overexpressed H 2 O 2 into highly oxidized hydroxyl radicals (•OH). The heat induced by PTT also relieved the intratumoral hypoxia to sensitize RT. Consequently, this TME-responsive precise nanoradiosensitization achieved improved irradiation effectiveness, potent oxygenation in tumor, and efficient suppression to tumor, which can be real-time monitored by computed tomography and photoacoustic imaging.

Adapting and Remolding: Orchestrating Tumor Microenvironment Normalization with Photodynamic Therapy by Size Transformable Nanoframeworks

“…Nanoscale materials have prevailing applications in assisting diverse therapeutic modalities owing to their tailor-able properties that can respond and accommodate to TME characteristics. [8][9][10][11] By manipulating the component size, structure hierarchy and surface chemistry,t he nanovehicles featuring size transformation in response to TME cues could circumvent the stroma-shaped penetration barrier, uplifting the effective dose of therapeutic agents in deep-seated tumor. [12][13][14] In this regard, developing versatile platform with controllable nanomaterials that are adaptive to therapeutic barriers in TME exhibits potent efficacy to kill tumor cells directly.H owever,m erely avoiding TME barriers in the transportation of therapeutic components is inadequate for the clearance of solid tumors.…”

MoS2-based nanocomposites for cancer diagnosis and therapy

“…Hafnium dioxide (HfO 2 ) nanoparticles have strong X-ray attenuation ability, and are regarded as potential radiosensitive agents. Recently, Fu et al [ 340 ] integrated MoS 2 , HfO 2 and dextran into new nanoplatforms (M/H-D) for CT/PA imaging-guided PTT/RT. HfO 2 produced ROS to kill cancer cells under X-ray irradiation.…”

Combined Application of Nanotechnology and Multiple Therapies with Tumor Immune Checkpoints

“…[70] The application of the nanometer drug delivery system to the combined treatment of immunological checkpoints and radiotherapy can effectively enhance the radiotherapy effect of diseased sites, and at the same time can be loaded with immunotherapy drugs to achieve synergistic therapy. [71] The carrier used for combined radiotherapy and immunotherapy should contain some inorganic metal nanoparticles, such as nanoparticles containing rare earth elements (rhenium oxide nanoparticles, up-conversion nanoparticles, etc. ); [72] and nanoparticles containing high atomic number elements (gold nanoparticles, Thorium oxide nanoparticles, etc.…”

“…Some nano‐materials can absorb radiation and act as radiosensitizers to deposit radiant energy in tumors to improve the treatment effect [70] . The application of the nanometer drug delivery system to the combined treatment of immunological checkpoints and radiotherapy can effectively enhance the radiotherapy effect of diseased sites, and at the same time can be loaded with immunotherapy drugs to achieve synergistic therapy [71] . The carrier used for combined radiotherapy and immunotherapy should contain some inorganic metal nanoparticles, such as nanoparticles containing rare earth elements (rhenium oxide nanoparticles, up‐conversion nanoparticles, etc.…”