Tetrahedral Framework Nucleic Acids Based Small Interfering RNA Targeting Receptor for Advanced Glycation End Products for Diabetic Complications Treatment

ACS Nano, Journal Year: 2023, Volume and Issue: 17(22), P. 22668 - 22683

Published: Sept. 26, 2023

Complications arising from diabetes can threaten multiple organs. Advanced glycation end products (AGEs) play a significant role in inducing these complications. Highly processed diets and hyperglycemia facilitate the accumulation of AGEs body. Interaction between their main receptor (RAGE) initiates transmission intracellular inflammatory cell death signals, which ultimately lead to To counter AGEs-induced damage, we developed an siRNA-binding tetrahedral framework nucleic acids (TDN) system, termed Tsi, combines potent membrane penetrability serum stability TDN with gene-targeting specificity siRNA-RAGE. Tsi effectively persistently downregulates expression RAGE, thereby suppressing inflammation by blocking NF-κB pathway as well exhibiting antioxidant functions. Furthermore, regulates pyroptosis state macrophages via NLRP3/caspase-1 axis, inhibits spread signals maintains homeostasis. This is great significance for synergistic treatment strategy systemic complications patients refractory hyperglycemia. In summary, this study describes nanomedicine that targets RAGE suppresses AGE-induced inflammation. acid drug holds long-lasting efficacy independent lowering hyperglycemia, provides diabetic age-related diseases.

Language: Английский

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A Transdermal Drug Delivery System Based on Nucleic Acid Nanomaterials for Skin Photodamage Treatment

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(46)

Published: July 9, 2023

Abstract Skin photodamage, which is induced by ultraviolet (UV) radiation, a prevalent cause of skin damage. In this study, transdermal drug delivery system developed for the topical treatment composed tetrahedral framework nucleic acids (tFNAs) and lipoic acid (LA). The tFNAs‐LA (TLA) nanocomposite exhibits excellent biocompatibility, as well antioxidant, anti‐apoptotic, anti‐inflammatory capabilities. tFNA, carrier, facilitates TLA cell entry penetration, while loaded LA enhances antioxidant photodamaged human dermal fibroblast (HDF), promotes proliferation migration inhibiting apoptosis activation reactive oxygen species production. Moreover, modulates apoptosis‐related proteins NF‐κB signaling pathways, increasing cellular secretion suppressing inflammatory responses in HDF cells. vivo experiment, application tissue healing skin, regulates expression inflammation collagen‐related proteins. It suggested that ability enables non‐invasive therapy highlighting potential employing acid‐based systems disease.

Language: Английский

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Inhalable pH-responsive DNA tetrahedron nanoplatform for boosting anti-tumor immune responses against metastatic lung cancer

Biomaterials, Journal Year: 2023, Volume and Issue: 301, P. 122283 - 122283

Published: Aug. 24, 2023

Language: Английский

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Synergistic Brilliance: Engineered Bacteria and Nanomedicine Unite in Cancer Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 24, 2024

Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, producing anticancer microbial agents situ to suppress growth. Despite the unique advantages of bacteria-based biotherapy, insufficient efficiency limits its application complete ablation malignant tumors. The combination nanomedicine engineered has attracted increasing attention owing their striking synergistic effects treatment. that function as natural vehicles effectively deliver nanomedicines sites. Moreover, provide an opportunity enhance by modulating TME substrates support nanomedicine-mediated reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, catalytic properties, plays important role promoting bacteria-mediated biotherapies. therapy comprehensively summarized this review. Attention is paid not only fabrication nanobiohybrid composites, but also interpromotion mechanism between therapy. Additionally, recent advances bacteria-synergized multimodal therapies highlighted.

Language: Английский

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Bone tissue engineering based on sustained release of MiR29c-modified framework nucleic acids from an injectable hydrogel

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 487, P. 150706 - 150706

Published: March 25, 2024

Language: Английский

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Circular RNA‐based neoantigen vaccine for hepatocellular carcinoma immunotherapy

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 29, 2024

Abstract mRNA vaccines are regarded as a highly promising avenue for next‐generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence linear significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer novel solution to these limitations due efficient protein ability, which can be rapidly generated in vitro without need extra modifications. Here, we present neoantigen vaccine based on circRNA that induces potent anti‐tumor immune response by expressing hepatocellular carcinoma‐specific tumor neoantigens. By cyclizing linearRNA molecules, were able enhance stability RNA form stable molecules with capacity sustained expression. We confirmed neoantigen‐encoded promote dendritic cell (DC) activation DC‐induced T‐cell vitro, thereby enhancing killing cells. Encapsulating within lipid nanoparticles vivo has enabled creation platform. This platform demonstrates superior treatment prevention various murine models, eliciting robust response. Our offers new options application prospects immunotherapy solid tumors.

Language: Английский

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A Bioswitchable MiRNA Delivery System: Tetrahedral Framework DNA-Based miRNA Delivery System for Applications in Wound Healing

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(26), P. 33192 - 33204

Published: June 17, 2024

The human body's primary line of defense, the skin, is especially prone to harm. Although microRNA (miRNA)-based therapies have attracted increasing attention for skin wound healing, their applications remain limited owing a range issues. Tetrahedral framework DNA (tFNA), nanomaterial possessing nucleic acid characteristics, exhibits an excellent biocompatibility, in addition anti-inflammatory and transdermal delivery capabilities, can accelerate healing. Due its potential exert synergistic action with therapeutic miRNA, tFNA has been considered ideal vehicle miRNA therapy. design synthesis bioswitchable system (BiRDS) reported, which contains three miRNAs as well core maximize loading capacity while preserving characteristics tFNA. A high stability, permeability cells tissues good biological compatibility are demonstrated. By selectively inhibiting heparin-binding epidermal growth factor (HB-EGF), BiRDS inhibit NF-κB pathway simultaneously controlling PTEN/Akt pathway. As result, helps healing go through inflammation proliferative phase. This study demonstrates advantages miRNA-based therapy provides new research ideas treatment skin-related diseases.

Language: Английский

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Programmable Tetrahedral DNA‐RNA Nanocages Woven with Stimuli‐Responsive siRNA for Enhancing Therapeutic Efficacy of Multidrug‐Resistant Tumors

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 25, 2024

Abstract Multidrug resistance (MDR) is a major obstacle limiting the effectiveness of chemotherapy against cancer. The combination strategy chemotherapeutic agents and siRNA targeting drug efflux has emerged as an effective cancer treatment to overcome MDR. Herein, stimuli‐responsive programmable tetrahedral DNA‐RNA nanocages (TDRN) have been rationally designed developed for dynamic co‐delivery doxorubicin P‐glycoprotein (P‐gp) siRNA. Specifically, sense antisense strand sequences P‐gp siRNA, which are bricks with terminal disulfide bond conjugation, precisely embedded in one edge DNA tetrahedron. TDRN provides release element control functional cargo that significantly more stable than “tail‐like” TDN nanostructures. highly rigid 3D nanostructure siRNA‐organized demonstrated notable improvement stability RNase A mouse serum, well long‐term storage up 4 weeks, evidenced by this study. These biocompatible multifunctional nanocarriers gold nanocluster‐assisted delivery (TDRN@Dox@AuNC p ) successfully used achieve synergistic RNAi/Chemo‐therapy vitro vivo. This system, integrates RNAi therapy chemotherapy, offers promising approach treating multidrug‐resistant tumors.

Language: Английский

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Osteochondral Interface: Regenerative Engineering and Challenges

ACS Biomaterials Science & Engineering, Journal Year: 2023, Volume and Issue: 9(3), P. 1205 - 1223

Published: Feb. 8, 2023

Osteochondral (OC) defects are debilitating for patients and represent a significant clinical problem orthopedic surgeons as well regenerative engineers due to their potential complications, which likely lead osteoarthritis related diseases. If they remain untreated or treated suboptimally, OC lesions known impact the articular cartilage transition from bone, that is, cartilage–bone interface. An important component of interface, selectively permeable membrane, tidemark, still remains unaddressed in more than 90% published research past decade. This review focuses on structure, composition, function engineering attempts with different scaffolding strategies challenges ahead us recapitulating native There schools thought regarding structure interface: stratified graded. The former assumes cartilage-to-bone interface be hierarchically divided into distinct yet continuous zones uncalcified cartilage–calcified cartilage–subchondral bone. latter is continuously graded, formed by an infinite number layers. cellular composition either respective layers changing graded manner, chondrocytes, hypertrophic osteoblasts moved Functionally, assumed play role enabling smooth loads exerted surface bone underneath. Regenerative involves, first, characterization terms function, and, then, proposes appropriate biomaterials, cells, biomolecules alone combination eventually form mimics functionally behaves similar major challenge regeneration appears lie, addition others, formation thin membrane separating two zones: avascular vascular amount literature approaches interface; however, only small portion them consider importance tidemark. Therefore, this aims at highlighting significance structural organization components increasing awareness orthopedics community tidemark after interventions attempts.

Language: Английский

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Liver-Targeted Delivery of Small Interfering RNA of C–C Chemokine Receptor 2 with Tetrahedral Framework Nucleic Acid Attenuates Liver Cirrhosis

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(8), P. 10492 - 10505

Published: Feb. 17, 2023

Liver cirrhosis is the end stage of chronic liver diseases without approved clinical drugs. In this study, a new strategy that uses C–C chemokine receptor 2 (CCR2) small interfering RNA silencing (siCcr2)-based therapy by loading multivalent siCcr2 with tetrahedron framework DNA nanostructure (tFNA) vehicle (tFNA-siCcr2) was established to attenuate fibrosis. tFNA-siCcr2 successfully synthesized changing physiochemical properties tFNA. Compared naked molecule, complex altered accumulation from kidney after intraperitoneal injection. The also prolonged hepatic retention and mainly colocalized within macrophages endothelial cells. efficiently silenced CCR2 significantly ameliorated fibrosis in prevention treatment interventions. Single-cell sequencing followed experimental validation suggested can restore immune cell landscape construct an antifibrotic niche inhibiting profibrotic macrophage neutrophil murine fibrotic liver. Molecularly, reduced inflammatory mediator production inactivating NF-κB signaling pathway. conclusion, tFNA-based liver-targeted delivery restoring constructing niche, which makes potential therapeutic candidate for cirrhosis.

Language: Английский

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