The promotion of nanoparticle delivery to two populations of gastric cancer stem cells by CD133 and CD44 antibodies.

Gastric cancer which starts from the stomach is a fatal cancer with poor prognosis around the world. The recurrence and metastasis of gastric cancer may be attributed to gastric cancer stem cells. It is recognized that cancer usually possesses multiple populations of distinct cancer stem cells with different phenotypes, thus it will be imperative to target more subsets of cancer stem cells instead of targeting only one population of cancer stem cells. It is generally accepted that both CD44 and CD133 are gastric cancer stem cells markers, we hereby developed CD44/CD133-ATRA-PLPN (CD44 and CD133 antibody-conjugated all-trans retinoic acid-loaded poly(lactide-co-glycolide)-lecithin-PEG nanoparticles) to target both CD133+ and CD44+ gastric cancer stem cells. In this study, the therapeutic effect of CD44/CD133-ATRA-PLPN against gastric cancer stem cells was investigated. The results presented here confirmed that CD44/CD133-ATRA-PLPN was efficiently and specifically delivered to CD44+ or CD133+ gastric cancer stem cells, resulting in enhanced growth inhibitory effect towards gastric cancer stem cells compared with single targeted and non-targeted nanoparticles. As far as we know, we firstly reported the promotion of nanoparticle delivery to two populations of gastric cancer stem cells by antibodies. Since cancer usually contains distinct populations of cancer stem cells with multiple phenotypes, our dual targeting nanoparticles constitute an effective drug delivery platform for targeting multiple populations of cancer stem cells within the cancer.

Autologous transplantation of endothelial progenitor cells to prevent multiple organ dysfunction syndromes in pig.

BACKGROUND: It was observed that the number and function of endothelial progenitor cells (EPCs) decreased sharply in the progression of multiple organ dysfunction syndrome (MODS), and it may be the main pathogenesis for MODS. We aim to perform autologous transplantation of EPCs on animal models of MODS to investigate whether EPCs might be used to prevent MODS caused by severe sepsis. METHODS: A total of 60 pigs were randomly divided into three groups: subjected to hemorrhagic shock + resuscitation + endotoxemia only (MODS group); performed autologous transplantation of EPCs after hemorrhagic shock + resuscitation + endotoxemia (transplantation group); and control group. Mononuclear cells of animals of the transplantation group were isolated by density-gradient centrifugation for ex vivo expansion, and the six-passage EPCs labeled with 5-carboxyfluorescein diacetate succinimidyl ester were autologously transplanted at a density of 1 × 10(7) cells/kg body weight at the 24th hour after endotoxemia. The function of important organs was monitored continuously to assess the effects of autologous transplantation of EPCs on MODS. RESULTS: All animals of the MODS group developed MODS (100%), and 17 (85%) of 20 animals died because of MODS; the incidence of MODS and mortality rate in the transplantation group were 45% (9 of 20 pigs; p < 0.01) and 35% (7 of 20 pigs; p < 0.01). In transplantation group, the incidence of pulmonary dysfunction, cardiac dysfunction, hepatosis, and renal dysfunction were 40%, 10%, 5%, and 15%, respectively. The capillary densities of important organs, including the heart, liver, kidney, intestine, and lung, after autologous transplantation of EPCs were significantly higher than those in the MODS group (p < 0.01). CONCLUSION: Autologous transplantation of EPCs could migrate to injured organs and induce angiogenesis to restore blood flow that could improve the function of important organs. It could prevent the incidence of MODS and reduce mortality rate caused by trauma and severe sepsis. Autologous transplantation of EPCs would be a novel, cell-based, vascular endothelium-targeted therapeutic strategy for MODS.