Obesity-induced insulin resistance is the hallmark of metabolic syndrome, and chronic, low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Current therapeutic approaches lack efficacy and immunomodulatory capacity. Thus, a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance. Here, we synthesized a tetrahedral framework nucleic acid (tFNA) nanoparticle that carried resveratrol (RSV) to inhibit tissue inflammation and improve insulin sensitivity in obese mice. The prepared nanoparticles, namely tFNAs-RSV, possessed the characteristics of simple synthesis, stable properties, good water solubility, and superior biocompatibility. The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy. In high-fat diet (HFD)-fed mice, the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status. tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages. As for adaptive immunity, the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg, leading to the alleviation of insulin resistance. Furthermore, this study is the first to demonstrate that tFNAs, a nucleic acid material, possess immunomodulatory capacity. Collectively, our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice, suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

No abstract

In a search for a solution to large-area soft and hard tissue defects, whether or not tissue regeneration or tissue-substitutes transplantation is used, the problems with angiogenesis need to be solved urgently. Thus, a new and efficient proangiogenic approach is needed. Nanoengineering systems have been considered one of the most promising approaches. In this study, we modify the tetrahedral framework nucleic acid (tFNA) for the first time with two different angiogenic DNA aptamers to form aptamer–tFNA nanostructures, tFNA–Apt02 and tFNA–AptVEGF, and the effects of them on angiogenesis both in vitro and in vivo are investigated. We develop new nanomaterials for enhancing angiogenesis to solve the problem of tissue engineering vascularization and ischemic diseases. The results of our study confirm that tFNA–Apt02 and tFNA–AptVEGF has a stronger ability to accelerate endothelial cell proliferation and migration, tubule formation, spheroid sprouting, and angiogenesis in vivo. We first demonstrate that the engineered novel tFNA–Apt02 and tFNA–AptVEGF have promoting effects on angiogenesis both in vitro and in vivo and provide a theoretical basis and opportunity for their application in tissues engineering vascularization and ischemic diseases.