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.
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.
The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients’ life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
Conventional
antiangiogenetic inhibitors suffered from poor delivery
problems that result in unsatisfactory antitumor treatment efficacy.
Although the liposomes or nanomaterial-based delivery systems can
improve the therapeutic efficacy of antiangiogenic molecules, the
assembly process is far too complex. Herein, a nanomaterial or a new
nanodrug that could work without the help of a carrier and could be
easily synthesized is needed. Au nanoclusters (AuNCs) are a kind of
ideal nanostructures that could spontaneously enter into the cell
and could be synthesized by a relatively easy one-pot method. Here,
changing the traditional ligand glutathione (GSH) into an anti-Flt1
peptide (AF) has enriched the newly synthesized AF@AuNCs with targeted
antiangiogenic properties. Based on the specific binding between AF
and vascular endothelial growth factor receptor 1 (VEGFR1), the interaction
between VEGFR1 and its ligands could be blocked. Furthermore, the
expression of VEGFR2 could be downregulated. Compared with pure AF
peptide- and GSH-participated AuNCs (GSH@AuNCs), AF@AuNCs were more
effective in inhibiting both tube formation and migration of the endothelial
cells in vitro. Furthermore, the in vivo chick embryo chorioallantoic
membrane (CAM) experiment and antitumor experiment were conducted
to further verify the enhanced antiangiogenesis and tumor inhibition
effect of AF@AuNCs. Our findings provide promising evidence of a carrier-free
nanodrug for tumors and other vascular hyperproliferative diseases.
This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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