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Atherosclerosis, a major global health concern with high morbidity and mortality rates, involves complex interactions of chronic inflammation, oxidative stress, and proteolytic enzymes. Conventional imaging methods struggle to capture the dynamic biochemical processes in atherosclerotic plaques. Here, we introduce a novel unimolecular photoacoustic probe (UMAPP) designed with specific binding sites for neutrophil elastase (NE) and the redox pair O2⋅−/GSH, enabling real‐time monitoring of oxidative stress and activated neutrophils in plaques. UMAPP, comprising a boron‐dipyrromethene (BODIPY) core linked to a hydrophilic NE‐cleavable tetrapeptide and dual oxidative stress‐responsive catechol moieties, facilitates NE‐mediated modulation of photoinduced electron transfer impacting photoacoustic intensity at 685 nm (PA685). Furthermore, oxidation and reduction of catechol groups by O2⋅− and GSH induce reversible, ratiometric changes in the photoacoustic spectrum (PA745/PA685 ratio). Initial UMAPP applications successfully distinguished atherosclerotic and healthy mice, evaluated pneumonia's effect on plaque composition and verified the probe's effectiveness in drug‐treatment studies by detecting molecular alterations before visible histopathological changes. The integrated molecular imaging capabilities of UMAPP offer promising advancements in atherosclerosis diagnosis and management, enabling early and accurate identification of vulnerable plaques. [ABSTRACT FROM AUTHOR]

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia‐induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core‐shell nanoparticles (PM‐CS NPs). Owing to the good carrier of O2 as fuel, PM‐CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM‐CS NPs exhibit the "turn on" 19F‐MRI signal and activatable T1/T2‐MRI contrast for correlating with the release of Mn. Finally, PM‐CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2‐mediated enhancement of key pathways of ferroptosis. [ABSTRACT FROM AUTHOR]

Molybdenum oxide (MoOx) nanosheets with high near-infrared (NIR) absorbance and pH-dependent oxidative degradation properties were synthesized, functionalized with polyethylene glycol (PEG), and then used as a degradable photothermal agent and drug carrier. The nanosheets, which are relatively stable under acidic pH, could be degraded at physiological pH. Therefore, MoOx-PEG distributed in organs upon intravenous injection would be rapidly degraded and excreted without apparent in vivo toxicity. MoOx-PEG shows efficient accumulation in tumors, the acidic pH of which then leads to longer tumor retention of those nanosheets. Along with the capability of acting as a photothermal agent for effective tumor ablation, MoOx-PEG can load therapeutic molecules with high efficiencies. This concept of inorganic theranostic nanoagent should be relatively stable in tumors to allow imaging and treatment, while being readily degradable in normal organs to enable rapid excretion and avoid long-term retention/toxicity. [ABSTRACT FROM AUTHOR]