Recent Progress on Tumor Microenvironment-Activated NIR-II Phototheranostic Agents with Simultaneous Activation for Diagnosis and Treatment.

Malignant tumors seriously threaten human life and well-being. Emerging Near-infrared II (NIR-II, 1000-1700 nm) phototheranostic nanotechnology integrates diagnostic and treatment modalities, offering merits including improved tissue penetration and enhanced spatiotemporal resolution. This remarkable progress has opened promising avenues for advancing tumor theranostic research. The tumor microenvironment (TME) differs from normal tissues, exhibiting distinct attributes such as hypoxia, acidosis, overexpressed hydrogen peroxide, excess glutathione, and other factors. Capitalizing on these attributes, researchers have developed TME-activatable NIR-II phototheranostic agents with diagnostic and therapeutic attributes concurrently. Therefore, developing TME-activatable NIR-II phototheranostic agents with diagnostic and therapeutic activation holds significant research importance. Currently, research on TME-activatable NIR-II phototheranostic agents is still in its preliminary stages. This review examines the recent advances in developing dual-functional NIR-II activatable phototheranostic agents over the past years. It systematically presents NIR-II phototheranostic agents activated by various TME factors such as acidity (pH), hydrogen peroxide (H2 O2 ), glutathione (GSH), hydrogen sulfide (H2 S), enzymes, and their hybrid. This encompasses NIR-II fluorescence and photoacoustic imaging diagnostics, along with therapeutic modalities, including photothermal, photodynamic, chemodynamic, and gas therapies triggered by these TME factors. Lastly, the difficulties and opportunities confronting NIR-II activatable phototheranostic agents in the simultaneous diagnosis and treatment field are highlighted.

NIR-II Imaging-Guided Mitochondrial-Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy.

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.

A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy.

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.

[Mechanism of acupuncture anesthesia for analgesia of the operative region of thyroid gland].

OBJECTIVE: To probe into peripheral nervous mechanisms of analgesic effect of electroacupuncture (EA) at Hegu (LI 4) and Neiguan (PC 6) on cervical region. METHODS: Twenty cases of thyroid disease who wished to receive acupuncture anesthesia, were stimulated with electroacupuncture at bilateral Hegu (LI 4), Neiguan (PC 6) in continued wave, intensity of 6-8 V, frequency of 10-20 Hz. After stimulation for 40 min, the operation was made. Before EA stimulation, 10 min, 20 min and 30 min after EA stimulation, changes of the physiologi cal functions including latent period, conduction velocity, wave peak amplitude of great auricular nerve were monitored and changes of pain sense were detected. RESULTS: After EA given at Hegu (LI 4) and Neiguan (PC 6) for 10 min, 20 min and 30 min, the pain sense significantly decreased (P<0.01), the latent period of great auricular nerve was shortened, and the conduction velocity was fastened and the wave peak amplitude raised with significant changes as compared with those before EA stimulation (P<0.01). CONCLUSION: EA at Hegu (LI 4) and Neiguan (PC 6) can produce a better analgesic effect on cervical region; EA at Hegu (LI 4) and Neiguan (PC 6) induces electro-physio logic changes of the nerve innervating the cervical region, showing increase of excitability; the nerves innervating Hegu (LI 4) and Neiguan (PC 6) and the nerves of cervical region possibly are homologous nerves.