Hierarchical Multiplexing Nanodroplets for Imaging-Guided Cancer Radiotherapy via DNA Damage Enhancement and Concomitant DNA Repair Prevention

Abstract

Clinical success of cancer radiotherapy is usually impeded by a combination of two factors, i.e., insufficient DNA damage and rapid DNA repair during and after treatment, respectively. Existing strategies for optimizing the radiotherapeutic efficacy often focus on only one facet of the issue, which may fail to function in the long term trials. Herein, we report a DNA-dual-targeting approach for enhanced cancer radiotherapy using a hierarchical multiplexing nanodroplet, which can simultaneously promote DNA lesion formation and prevent subsequent DNA damage repair. Specifically, the ultrasmall gold nanoparticles encapsulated in the liquid nanodroplets can concentrate the radiation energy and induce dramatic DNA damage as evidenced by the enhanced formation of γ-H2AX foci as well as in vivo tumor growth inhibition. Additionally, the ultrasound-triggered burst release of oxygen may relieve tumor hypoxia and fix the DNA radical intermediates produced by ionizing radiation, prevent DNA repair, and eventually result in cancer death. Finally, the nanodroplet platform is compatible with fluorescence, ultrasound, and magnetic resonance imaging techniques, allowing for real-time in vivo imaging-guided precision radiotherapy in an EMT-6 tumor model with significantly enhanced treatment efficacy. Our DNA-dual-targeting design of simultaneously enhancing DNA damage and preventing DNA repair presents an innovative strategy to effective cancer radiotherapy.

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

“…Some gasotransmitters (e.g., O 2 , NO, H 2 S, etc.) can act as radiosensitizers to remarkably increase the sensitivity of the hypoxic cells to X‐ray radiation for enhanced RT efficacy, which leads to synergistic RT/gas therapy. Moreover, the ROS arising from PDT can inhibit the DNA repair of cancer cells following exposure to RT, which provides an opportunity for synergistic RT/PDT.…”

Reversing Immunosuppression in Hypoxic and Immune‐Cold Tumors with Ultrathin Oxygen Self‐Supplementing Polymer Nanosheets under Near Infrared Light Irradiation

“…We then examined the capability of nanosheets to catalyze O 2 generation and ROS production in 4T1 cells cultured in a hypoxia chamber flushed with humidified 1% O 2 , 5% CO 2 and 94% N 2 . [ 51 ] Following staining with a hypoxia probe of pimonidazole hydrochloride, we observed an apparent relief of hypoxia in 4T1 cells treated with nanosheets plus irradiation compared to the PBS group (Figure S15, the Supporting Information). Furthermore, both laser scanning confocal microscope (CLSM) observation and flow cytometry (FACS) analyses showed the efficient cellular production of ROS in a laser power density‐dependent manner, as evidenced by the elevated fluorescence signals of the ROS sensor 2′,7′‐dichlorodihydrofluorescein diacetate (DCFH‐DA) ( Figure a,b; Figure S16, the Supporting Information).…”

Materdicine: Interdiscipline of materials and medicine

“…Furthermore, triggered by various endogenous and/or exogenous stimuli (eg, pH, light, and temperature), the engineered intelligent nanoplatforms can implement controllable release of chemotherapeutic drugs or therapeutic elements, which avoid drug leakage in normal tissues and mitigate potential side effects 85 . In consequence, ever‐increasing research efforts have been dedicated to using nanomedicine and nanobiotechnology to engineer high‐performance nanomaterials for disease therapies, including chemotherapy, 86 PDT, 87 PTT, 88 radiotherapy, 89 MHT, 90 US‐based therapy, 91 and other treatment modalities 92 …”