Despite widespread applications for cancer treatment, chemotherapyisrestricted by several limitations,including low targeting specificity,a cquired drug resistance,a nd concomitant adverse side effects.I tr emains challenging to overcome these drawbacks. Herein, we report an ew bioenergetic approach for treating cancer efficiently.Asaproof-ofconcept, we construct activatable mitochondria-targeting organoarsenic prodrugs from organoarsenic compounds and traditional chemotherapeutics.T hese prodrugs could accomplish selective delivery and controlled release of both therapeutic agents to mitochondria, which synergistically promote mitochondrial ROS production and induce mitochondrial DNA damage,finally leading to mitochondria-mediated apoptosis of cancer cells.O ur in vitro and in vivo experiments reveal the excellent anticancer efficacy of these prodrugs,u nderscoring the encouraging outlook of this strategy for effective cancer therapy.
In vivo levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are critical to many physiological and pathological processes. Because of the distinct differences in their biological generation and effects, simultaneously visualizing both of them could help deepen our insights into the mechanistic details of these processes. However, real-time and deep-tissue imaging and differentiation of ROS-and RNS-related molecular events in living subjects still remain a challenge. Here, we report the development of two activatable 19 F magnetic resonance imaging (MRI) molecular probes with different 19 F chemical shifts and specific responsive behaviors for simultaneous in vivo detection and deep-tissue imaging of O 2•− and ONOO − . These probes are capable of real-time visualization and differentiation of O 2•− and ONOO − in living mice with drug-induced acute kidney injury by interference-free multiplexed hot-spot 19 F MRI, illustrating the potential of this technique for background-free real-time imaging of diverse biological processes, accurate diagnosis of various diseases in deep tissues, and rapid toxicity evaluation of assorted drugs.
The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin-cooperated human serum albumin (HSA)-GGD-ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic-acid-modified gadolinium (III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA-GGD-ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA-GGD-ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real-time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin-mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.
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