Tetrahedral framework nucleic acids/hyaluronic acidmethacrylic anhydride hybrid hydrogel with antimicrobial and anti-inflammatory properties for infected wound healing

Bacterial resistance and excessive inflammation are common issues that hinder wound healing.Antimicrobial peptides(AMPs)offer a promising and versatile antibacterial option compared to traditional antibiotics,with additional anti-inflammatory properties.However,the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation.TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs.Therefore,in this study,a composite hydrogel(HAMA/t-GL13K)was prepared via the photocross-linking method,in which tFNAs carry GL13K.The hydrogel was injectable,biocompatible,and could be instantly photocured.It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS.Thereby,the hydrogel inhibited bacterial infection,shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring.The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

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.

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis

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,t FNA-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.

Correction to:Tetrahedral Framework Nucleic Acid‑Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Correction to:Nano‑Micro Lett.(2021)13:86 https://doi.org/10.1007/s40820-021-00614-6 The Nano-Micro Letters(2021)13:86,article by Li et al.,entitled“Tetrahedral Framework Nucleic Acid‐Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity”(Nano-Micro Lett.https://doi.org/10.1007/s40820-021-00614-6),was published online 06 March,2020,with errors.

Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis

Gouty arthritis is a very familiar inflammatory arthritis.Controlling inflammation is the key to preventing gouty arthritis.However,colchicine,the most highly represented drug used in clinical practice,has strict contraindications owing to some severe side effects.Curcumin(Cur),a natural anti-inflammatory drug,has demonstrated good safety and efficacy.However,the rapid degradation,poor aqueous solubility,and low bioavailability of Cur limit its therapeutic effect.To strengthen the effectiveness and bioavailability of Cur.Cur loaded tetrahedral framework nucleic acids(Cur-TFNAs)were synthesized to deliver Cur.Compared with free Cur,Cur-TFNAs exhibit a preferable drug stability,good biocompatibility(CCK-8 assay),ease of uptake(immunofluorescence),and higher tissue utilization(in vivo biodistribution).Most importantly,Cur-TFNAs present better anti-inflammatory effect than free Cur both in vivo and in vitro experiments through the determination of inflammation-related cytokines expression.Therefore,we believe that Cur-TFNAs have great prospects for the prevention of gout and similar inflammatory diseases.

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

While the skin is considered the first line of defense in the human body,there are some vulnerabilities that render it susceptible to certain threats,which is an issue that is recognized by both patients and doctors.Cutaneous wound healing is a series of complex processes that involve many types of cells,such as fibroblasts and keratinocytes.This study showed that tetrahedral framework nucleic acids(tFNAs),a type of self-assembled nucleic-acid material,have the ability to promote keratinocyte(HaCaT cell line)and fibroblast(HSF cell line)proliferation and migration in vitro.In addition,tFNAs increased the secretion of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in HSF cells and reduced the production of tumor necrosis factor-alpha(TNF-α)and interleukin-1 beta(IL-1β)in HaCaT cells by activating the AKT-signaling pathway.During in vivo experiments,tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars,compared with the control treatment that did not use tFNAs.This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring,which indicates the potential application of tFNAs in skin tissue regeneration.

Tetrahedral framework nucleic acids regulate osteogenic differentiation potential of osteoporotic adipose-derived stem cells

Osteoporosis(OP)is a noncommunicable bone disease caused by a shift in the balance between os-teoblasts and osteoclasts,and can severely affect the health of elderly persons.Autologous stem-cell transplantation can improve reduced bone density and weakened fracture healing abilities in patients with OP.However,OP can adversely affect the osteogenesis and proliferation abilities of autologous adipose-derived stem cells(ASCs).Therefore,an effective drug is required to facilitate autologous ASCs to recover their osteogenic and proliferative potential.Tetrahedral framework nucleic acid(tFNA)is a new type of nanomaterial that has ability to regulate the biological behavior of cells effectively and en-hance the bioactivity of stem cells.In this study,we examine the effects of tFNAs on the osteogenic differentiation and proliferation abilities of ASCs in rats with OP.The results indicate that the 250 nmol/L tFNAs can considerably increase the expression of osteogenesis-related markers,effectively promote the proliferation and osteogenic differentiation of osteoporotic ASCs(OP-ASCs),and help them to regain their osteogenic and proliferative potential.In short,tFNAs can enable OP-ACSs to recover their osteogenic po-tential and promote their proliferation and,therefore,can play a key regulatory role in autologous ASC transplantation.