Background Mitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge. Methods Herein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core. Results Inside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo. Conclusions This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.
Background: Lymph node metastasis (LNM) plays a vital role in the determination of clinical outcome in patients with gastric neuroendocrine tumor (G-NET). Preoperative identification of LNM is helpful for intraoperative lymphadenectomy. This study aims to investigate risk factors for LNM in patients with G-NET. Method: We performed a retrospective study involving 37 patients in non-LNM group and 82 patients in LNM group. Data of demographics, preoperative lab result, clinical pathological results, surgical management and postoperative situation were compared between groups. Significant parameters were subsequently entered into logistic regression for further analysis. Results: Patients in LNM group exhibited older age (p=0.011), lower preoperative albumin (ALB) (p=0.003), higher carcinoembryonic antigen (CEA) (p=0.020), higher International normalized ratio (p=0.034), longer thrombin time (p=0.018), different tumor location (p=0.005), higher chromogranin A positive rate (p=0.045), and higher Ki-67 expression level (p=0.002). Logistic regression revealed ALB (p=0.043), CEA (p=0.032), tumor location (p=0.013) and Ki-67 (p=0.041) were independent risk factors for LNM in G-NET patients. Conclusions: ALB, CEA, tumor location and Ki-67 expression level correlate with the risk of LNM in patients with G-NET.
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