Enhancement of ultralow-intensity NIR light-triggered photodynamic therapy based on exo- and endogenous synergistic effects through combined glutathione-depletion chemotherapy.

Although photodynamic therapy (PDT), which uses a photosensitizer (PS) to generate toxic reactive oxygen species (ROS) upon laser irradiation to kill cancer cells, has been widely applied, the relatively high laser intensity required causes photodamage to healthy neighboring cells and limits its success. Furthermore, glutathione (GSH, an antioxidant) is overexpressed in cancer cells, which can scavenge the generated ROS, thus lowering PDT efficacy. Herein, ultralow-intensity near-infrared (NIR) light-triggered PDT was developed and enhanced through combined GSH-depletion chemotherapy (Chemo) based on exo- and endogenous synergistic effects. Highly emissive upconversion nanoparticles (UCNPs) were prepared and coated with a solid silica shell, which was used to encapsulate the PS rose bengal and bond the drug camptothecin with a disulfide-bond linker. The combination of highly emissive UCNPs and a matchable PS with an optimized loading dosage enabled ROS to be generated for PDT even upon 808 nm laser irradiation with ultralow intensity (0.30 W cm-2). According to the American National Standard, this laser intensity is below the maximum permissible exposure of skin (MPE, 0.33 W cm-2). Once the prepared nanoparticles endocytosed and encountered intracellular GSH, the disulfide-bond linker was cleaved by GSH, leading to drug release and GSH depletion. PDT was therefore simultaneously enhanced through the exogenous synergic effect of Chemo (namely, the "1 + 1 > 2" therapeutic effect) and the endogenous synergic effect as a result of GSH depletion. It was proven both in vitro and in vivo that this novel dual-synergistic Chemo/PDT system exhibits remarkable therapeutic efficacy with minimal photodamage to healthy neighboring cells.

[Diagnostic value of serum CEACAM1 in patients with pancreatic cancer].

OBJECTIVE: To investigate the diagnostic value of serum CEACAM1 in patients with pancreatic cancer. METHODS: Fifty patients with pancreatic cancer and 50 with chronic pancreatitis were examine for serum levels of CEACAM1 by enzyme-linked immunosorbent assay (ELISA). The cut-off values and area under curve (AUC) of CEACAM1 was obtained by receiver operating characteristic (ROC) curve. The diagnostic efficiency of the tumor markers for pancreatic cancer was assessed by the fourfold table. RESULTS: The serum level and positivity rate of CEACAM1 in pancreatic cancer patients were higher than those in chronic pancreatitis patients (P<0.05). Based on the ROC curve, the cut-off values and AUC of CEACAM1 were 13.835 ng/ml and 0.780, respectively (P<0.05). In pancreatic cancer patients, the diagnostic sensitivities of the tumor markers decreased in the order of CEACAM1 < CA242 < CA19-9 (P<0.05), and the specificity in the order of CA242 < CA19-9 < CEACAM1 (P<0.05). CONCLUSION: CEACAM1 shows a higher diagnostic sensitivity than CA19-9 and CA242 for pancreatic cancer, but due to its low specificity this marker alone is not sufficient for diagnostic purposes.