Accurate diagnosis and effective treatment of malignant tumors under the interference of complex and diverse tumor microenvironments (TMEs) have become the focus of research. Herein, an innovative TME-activated biomimetic nanocatalyst with quad-modal imaging capabilities of second near-infrared (NIR-II) “turn-on” fluorescence imaging, magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal imaging (PTI) was designed and developed for self-enhanced photothermal/chemodynamic synergistic therapy. The catalyst was fabricated by loading glucose oxidase (GOD) and Ag2S quantum dots (QDs) on MnO2 nanosheets and coating them with a 4T1 cell membrane (AMG@CM), which enables them to successfully escape immune clearance and have appealing tumor-targeting ability and biocompatibility. The NIR-II fluorescence at 1130 nm of Ag2S QDs quenched by MnO2 could be recovered in vivo through the glutathione (GSH)-induced degradation of MnO2, enabling excellent TME-responsive tumor visualization. Simultaneously, the released Mn2+ can catalyze H2O2 to produce abundant hydroxyl radicals (•OH), achieving photothermal synergistically enhanced chemodynamic therapy (CDT) under NIR-II radiation. Moreover, the CDT could be self-enhanced by GOD due to the extra produced H2O2. This work demonstrates a novel and highly efficient multimodal imaging-guided integrated treatment strategy for dual-enhanced CDT tumor precise diagnosis and treatment.

Locus coeruleus (LC) sends widespread outputs to many brain regions to modulate diverse functions, including sleep/wake states, attention, and the general anesthetic state. The paraventricular thalamus (PVT) is a critical thalamic area for arousal and receives dense tyrosine-hydroxylase (TH) inputs from the LC. Although anesthesia and sleep may share a common pathway, it is important to understand the processes underlying emergence from anesthesia. In this study, we hypothesize that LC TH neurons and the TH:LC-PVT circuit may be involved in regulating emergence from anesthesia. Only male mice are used in this study. Here, using c-Fos as a marker of neural activity, we identify LC TH expressing neurons are active during anesthesia emergence. Remarkably, chemogenetic activation of LC TH neurons shortens emergence time from anesthesia and promotes cortical arousal. Moreover, enhanced c-Fos expression is observed in the PVT after LC TH neurons activation. Optogenetic activation of the TH:LC-PVT projections accelerates emergence from anesthesia, whereas, chemogenetic inhibition of the TH:LC-PVT circuit prolongs time to wakefulness. Furthermore, optogenetic activation of the TH:LC-PVT projections produces electrophysiological evidence of arousal. Together, these results demonstrate that activation of the TH:LC-PVT projections is helpful in facilitating the transition from isoflurane anesthesia to an arousal state, which may provide a new strategy in shortening the emergence time after general anesthesia.

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Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo . In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.

The effects of poly(ethylene glycol) (PEG) on improving the biological compatibility and circulation time of nanocarriers are determined by the surface density of PEG on nanoparticles. PEG with high surface density on nanocarriers has greater accumulation in tumor tissues. However, this impairs the release of drugs loaded in the nanoparticles in the tumor tissues. The relations and internal regularities between the controlled stripping of PEG of nanoparticles and its fate and antitumor efficacy in vivo remain unsolved. Redox-sensitive hybrid nanoparticles coated with varied PEG densities were prepared by blending a redox-sensitive polymer of DLPE-SS-MPEG. To keep identical nanoproperties, these nanoparticles were prepared with a similar size distribution of around 100 nm. The effects of controlled stripping of PEG on antitumor activities of nanoparticles were then investigated. As the PEG surface density increased, lower cellular internalization by tumor cells was observed. However, nanoparticles with higher controlled stripping of PEG showed greater accumulation in tumor tissues and advanced antitumor activities in vivo.