Search

The instinctive protective stress responses of tumor cells hamper low-temperature photothermal therapy (LTPTT), resulting in tumor recurrence and metastasis. The rapid blood clearance and low-efficiency tumor enrichment of nanomedicines also decrease the efficacy of LTPTT. In this study, we fabricated coassembled photothermal agents (indocyanine green, ICG) and autophagy inhibitors (chloroquine, CQ) and red blood cell and cancer cell hybrid membrane (RCm)-camouflaged ICGCQ@RCm nanoparticles (ICGCQ@RCm NPs) to enhance tumor LTPTT. The ICGCQ@RCm NPs exhibited prolonged blood drug circulation and markedly enhanced drug accumulation in tumor tissues. The ICGCQ@RCm NPs reduced the thermal tolerance of tumor cells to sensitize ICG-mediated LTPTT by inhibiting protective autophagy. The ICGCQ@RCm NPs exerted strong immunogenic cell death (ICD) after efficient LTPTT to activate antitumor immunity. In addition, ICGCQ@RCms optimized the therapeutic efficacy by imaging-guided LTPTT, taking advantage of the near-infrared (NIR) fluorescence of ICG. Consequently, the ICGCQ@RCm NPs effectively inhibited tumors under mild LTPTT, significantly suppressed tumor metastasis and prolonged the survival time of tumor-bearing mice. Furthermore, the ICGCQ@RCm NPs showed high biosafety in vitroand in vivo. The ICGCQ@RCm NPs demonstrated tumor-targeting and imaging-guided autophagy inhibition-sensitized LTPTT using two Food and Drug Administration (FDA)-approved drugs, which have great potential for clinical application.

Aim To investigate the relationship between epicardial adipose tissue (EAT) volume and coronary plaque composition.Methods EAT volume (measured using coronary computed tomography angiography) and coronary plaque characteristics were assessed on a per-segment basis (modified 15-segment American College of Cardiology/American Heart Association classification) in patients with severe coronary artery stenosis. Coronary plaques were classified into four types: 1, calcified plaques; 2, mixed plaques (calcification dominant); 3, mixed plaques (non-calcification dominant); and 4, non-calcified plaques. The gold standard for luminal stenosis was conventional coronary angiography.Results In 365 patients (mean age 58.7 ± 8.0 years), EAT volume was 169.85 ± 29.94 ml. There were no significant between-group differences in patient characteristics. Statistically significant differences in EAT volume between non-calcified and calcified plaque groups were observed. EAT volume showed a positive correlation with total cholesterol and low-density-lipoprotein cholesterol, and a very weak correlation with age, triglyceride, body mass index and high-density-lipoprotein cholesterol.Conclusion EAT volume was higher in the presence of non-calcified and mixed plaques in patients with ≥50% severe coronary artery stenosis.

The antioxidant defense system in malignant cells, which involves antioxidant enzymes and antioxidant molecules, is an innate barrier to photodynamic therapy (PDT). Because of the complexity of the endogenous antioxidant mechanisms of these cells, simply inhibiting individual antioxidant pathways has a limited effect on improving the lethality of ROS. To enhance the efficacy of PDT for tumor treatment, a versatile nanoparticle (NP)‐based drug is developed, which the authors call PZB NP, containing the glutathione inhibitor l‐buthionine sulfoximine (BSO) and the heme oxygenase 1 (HO‐1) inhibitor protoporphyrin zinc(II) (ZnPP) to suppress the innate antioxidant defense system of cancer cells in a two‐pronged manner. BSO reduces intracellular glutathione levels to minimize ROS elimination and protein protection during PDT, and ZnPP inhibits the ROS‐stimulated upregulation of the antioxidant HO‐1, thus preventing ROS removal by cells after PDT. Thus, BSO and ZnPP synergistically suppress the antioxidant defense systems of cancer cells both during and after protoporphyrin‐IX‐mediated PDT in a two‐pronged manner, resulting in tumor cell death through excess oxidative pressure. The results demonstrate that the construction of nanodrugs having dual antioxidation defense suppression properties is a promising route for the development of highly efficient ROS‐based therapies. A simple and versatile nanodrug, PZB nanoparticle, is developed to enhance PDT efficacy using a two‐pronged antioxidant suppression strategy. In short, the nanoparticle‐loaded BSO reduces the existing intracellular antioxidant (glutathione) concentration before PDT. Subsequently, the loaded protoporphyrin zinc(II) (ZnPP) inhibits ROS‐stimulated antioxidant enzymes (heme oxygenase 1) after PDT. These significantly enhance intracellular oxidative stress, leading to increased cancer cell death.