2 research outputs found

    Injectable Fullerenol/Alginate Hydrogel for Suppression of Oxidative Stress Damage in Brown Adipose-Derived Stem Cells and Cardiac Repair

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    Stem cell implantation strategy has exhibited potential to treat the myocardial infarction (MI), however, the low retention and survival limit their applications due to the reactive oxygen species (ROS) microenvironment after MI. In this study, the fullerenol nanoparticles are introduced into alginate hydrogel to create an injectable cell delivery vehicle with antioxidant activity. Results suggest that the prepared hydrogels exhibit excellent injectable and mechanical strength. In addition, the fullerenol/alginate hydrogel can effectively scavenge the superoxide anion and hydroxyl radicals. Based on these results, the biological behaviors of brown adipose-derived stem cells (BADSCs) seeded in fullerenol/alginate hydrogel were investigated in the presence of H<sub>2</sub>O<sub>2</sub>. Results suggest that the fullerenol/alginate hydrogels have no cytotoxicity effects on BADSCs. Moreover, they can suppress the oxidative stress damage of BADSCs and improve their survival capacity under ROS microenvironment via activating the ERK and p38 pathways while inhibiting JNK pathway. Further, the addition of fullerenol can improve the cardiomyogenic differentiation of BADSCs even under ROS microenvironment. To assess its therapeutic effects <i>in vivo</i>, the fullerenol/alginate hydrogel loaded with BADSCs were implanted in the MI area in rats. Results suggest that the fullerenol/alginate hydrogel can effectively decrease ROS level in MI zone, improve the retention and survival of implanted BADSCs, and induce angiogenesis, which in turn promote cardiac functional recovery. Therefore, the fullerenol/alginate hydrogel can act as injectable cell delivery vehicles for cardiac repair

    Zwitterionic-Modified Starch-Based Stealth Micelles for Prolonging Circulation Time and Reducing Macrophage Response

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    Over the last few decades, nanoparticles have been emerging as useful means to improve the therapeutic efficacy of drug delivery and medical diagnoses. However, the heterogeneity and complexity of blood as a medium is a fundamental problem; large amounts of protein can be adsorbed onto the surface of nanoparticles and cause their rapid clearance before reaching their target sites, resulting in the failure of drug delivery. To overcome this challenge, we present a rationally designed starch derivative (SB-ST-OC) with both a superhydrophilic moiety of zwitterionic sulfobetaine (SB) and a hydrophobic segment of octane (OC) as functional groups, which can self-assemble into “stealth” micelles (SSO micelles). The superhydrophilic SB kept the micelles stable against aggregation in complex media and imbued them with “stealth” properties, eventually extending their circulation time in blood. In stability and hemolysis tests the SSO micelles showed excellent protein resistance properties and hemocompatibility. Moreover, a phagocytosis test and cytokine secretion assay confirmed that the SSO micelles had less potential to trigger the activation of macrophages and were more suitable as a drug delivery candidate <i>in vivo</i>. On the basis of these results, doxorubicin (DOX), a hydrophobic drug, was used to investigate the potential application of this novel starch derivative <i>in vivo</i>. The results of the pharmacokinetic study showed that the values of the plasma area under the concentration curve (AUC) and elimination half-life (<i>T</i><sub>1/2</sub>) of the SSO micelles were higher than those of micelles without SB modifications. In conclusion, the combination of excellent protein resistance, lower macrophage activation, and longer circulation time <i>in vivo</i> makes this synthesized novel starch derivative a promising candidate as a hydrophobic drug carrier for long-term circulation <i>in vivo.</i