siRNA Delivery against Myocardial Ischemia Reperfusion Injury Mediated by Reversibly Camouflaged Biomimetic Nanocomplexes

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(23)

Published: March 13, 2023

siRNA-mediated management of myocardial ischemia reperfusion (IR) injury is greatly hampered by the inefficient enrichment and cardiomyocyte transfection. Herein, nanocomplexes (NCs) reversibly camouflaged with a platelet-macrophage hybrid membrane (HM) are developed to efficiently deliver Sav1 siRNA (siSav1) into cardiomyocytes, suppressing Hippo pathway inducing regeneration. The biomimetic BSPC@HM NCs consist cationic nanocore assembled from membrane-penetrating helical polypeptide (P-Ben) siSav1, charge-reversal intermediate layer poly(l-lysine)-cis-aconitic acid (PC), an outer shell HM. Due HM-mediated inflammation homing microthrombus targeting, intravenously injected can accumulate in IR-injured myocardium, where acidic inflammatory microenvironment triggers charge reversal PC shed off both HM layers allow penetration exposed P-Ben/siSav1 cardiomyocytes. In rats pigs, remarkably downregulates promotes myocardium regeneration, suppresses apoptosis, recovers cardiac functions. This study reports bioinspired strategy overcome multiple systemic barriers against delivery, holds profound potential for gene therapy injuries.

Language: Английский

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A Multifunctional Nanoparticle Mitigating Cytokine Storm by Scavenging Multiple Inflammatory Mediators of Sepsis

ACS Nano, Journal Year: 2023, Volume and Issue: 17(9), P. 8551 - 8563

Published: April 27, 2023

Sepsis is a disease caused by infection, which characterized dysregulated immune response in the host and affects more than 30 million people worldwide each year. However, current single therapeutic approaches are not effective controlling progression of sepsis. Here, we synthesize nanoparticle (TMP) containing tannic acid (TA), Polymyxin B (PMB), Mn2+ (Mn) simple one-pot method. TMP has following characteristics: (1) All components have good biocompatibility; (2) preparation process without subsequent processing; (3) antibacterial remove multiple inflammatory mediators; (4) effectively mitigating cytokine storm both acute lung injury (ALI) cecal ligation puncture (CLP) model. Our results demonstrate critical role targeting mediators to mitigate storms for treatment

Language: Английский

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Inflammation-Responsive Nanoagents for Activatable Photoacoustic Molecular Imaging and Tandem Therapies in Rheumatoid Arthritis

ACS Nano, Journal Year: 2024, Volume and Issue: 18(3), P. 2231 - 2249

Published: Jan. 8, 2024

Rheumatoid arthritis (RA) severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, representing a pressing public health concern. The pathogenesis of RA includes excessive production proinflammatory cytokines harmful oxygen-derived free radicals, such as nitric oxide (NO), which constitute vital targets for precise diagnosis effective treatment RA. In this study, we introduce an advanced nanoagent that integrates microenvironment-activatable photoacoustic (PA) imaging with multitarget synergistic A highly sensitive organic probe NO-tunable energy transformation molecular geometry is developed, enables strong near-infrared absorption turn-on PA signal, active intramolecular motion could further boost conversion. coassembled inflammation-responsive prodrug to construct theranostic nanoagent, on macrophage-derived cell membrane natural tropism inflammatory sites camouflaged improve targeting ability inflamed joints. not only sensitively detect differentiate severity but also efficiently alleviate symptoms function. combination activatable probe-mediated NO scavenging on-demand activation anti-inflammatory significantly inhibits factors promotes macrophage repolarization from M1 M2 phenotype. This meticulously designed ingeniously RA-specific therapy, rendering tremendous promise intervention RA-related diseases.

Language: Английский

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Helix-Guarded Molecular Clips for Cell-Free DNA Scavenging and Treatment of Systemic Lupus Erythematosus

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Immune disorders induced by cell-free DNA (cfDNA) account for the incidence and deterioration of systemic lupus erythematosus (SLE). Scavenging cfDNA using cationic polymers represents a promising modality SLE management. However, they bind mainly via electrostatic interaction, which would result in an undesired discharge captured upon competitive replacement negatively charged serum/intracellular components. Inspired natural recognition mechanism biomacromolecules spatial matching, we herein developed library dendrimer-templated, spherical, α-helical, guanidine-rich polypeptides as molecular clips scavenging. Upon optimization polypeptide length density on dendrimer surface, top-performing G3-8 was identified, could tightly confine within cavity between adjacent, rod-like α-helices. As thus, helical but not random-coiled analogue D,L-G3-8 enabled robust scavenging under serum-rich conditions to inhibit TLR9 activation inflammation. In mice, i.v. injected efficiently prevented organ failure inhibited inflammation cfDNA. This study provides enlightened strategy stably scavenge may shift current paradigm

Language: Английский

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An Optimally Designed Engineering Exosome–Reductive COF Integrated Nanoagent for Synergistically Enhanced Diabetic Fester Wound Healing

Small, Journal Year: 2022, Volume and Issue: 18(26)

Published: May 31, 2022

Abstract Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics reported widely, they are also challenged by pathogen contamination compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno‐engineered exosome (PCOF@E‐Exo) is to achieve efficient comprehensive combination therapy for wounds. The E‐Exo collected from TNF‐α‐treated mesenchymal stem cells (MSCs) under hypoxia encapsulated cationic antimicrobial carbon dots (CDs). This not only significantly scavenges reactive oxygen species induces anti‐inflammatory M2 macrophage polarization, but stabilizes hypoxia‐inducible factor‐1α (HIF‐1α). More importantly, the PCOF@E‐Exo exhibits intriguing bactericide capabilities toward Gram‐negative, Gram‐positive, drug‐resistant bacteria, showing favorable intracellular bacterial destruction biofilm permeation. In vivo results demonstrate that synergetic impact of suppressing oxidative injury tissue inflammation, promoting angiogenesis eradicating infection, could accelerate infected fester healing better therapeutic benefits than monotherapy or individual antibiotics. proposed strategy can inspire further research design more delicate platforms using immunotherapy other methods ulcerated wounds treatments.

Language: Английский

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Wielding the double-edged sword: Redox drug delivery systems for inflammatory bowel disease

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 358, P. 510 - 540

Published: May 16, 2023

Language: Английский

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Vesicular Antibodies: Shedding Light on Antibody Therapeutics with Cell Membrane Nanotechnology

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(12)

Published: Jan. 31, 2023

The high stability of antibodies and their ability to precisely bind antigens endogenous immune receptors, as well susceptibility protein engineering, enable antibody-based therapeutics be widely applied in cancer, inflammation, infection, other disorders. Nevertheless, the application traditional has certain limitations, such price, limited permeability, engineering complexity. Recent breakthroughs cell membrane nanotechnology have deepened understanding critical role receptors disease treatment, enabling vesicular-antibody-based therapeutics. Here, concept vesicular that are obtained by modifying target onto membranes for biomedical applications is proposed. Given an antibody basically a protein, extension this concept, vesicles or membrane-coated nanoparticles use surface on defined. Furthermore, several strategies summarized how can used variety situations highlighted. In addition, current challenges future prospects also discussed. It anticipated perspective will provide new insights development next-generation enhanced

Language: Английский

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Nanomedicine for T‐Cell Mediated Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(22)

Published: March 25, 2023

T-cell immunotherapy offers outstanding advantages in the treatment of various diseases, and with selection appropriate targets, efficient disease can be achieved. has made great progress, but clinical results show that only a small proportion patients benefit from immunotherapy. The extensive mechanistic work outlines blueprint for using T cells as new option immunotherapy, also presents challenges, including balance between different fractions cells, inherent suppression patterns microenvironment, acquired loss decline viability. diversity, flexibility, intelligence nanomedicines give them potential enhancing Here, how strategies adapted nanomaterials to enhance therapeutic efficacy is discussed. For two pathological states, immunosuppression immune activation, recent advances diseases such cancers, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, diabetes are summarized. With focus on this review highlights treatment, helps advance one's understanding use nanotechnology

Language: Английский

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Advanced Nanomedicine: Redefining Therapeutic Paradigms for Inflammatory Bowel Disease

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(19)

Published: March 16, 2023

Abstract Inflammatory bowel disease (IBD), a chronic and recurrent gastrointestinal inflammatory disorder with variety of painful clinical manifestations an increased risk cancerization or death, has become emerging challenge to global healthcare due its rapidly increasing incidence. At present, there is no efficient cure against IBD because the elusive etiology pathogenesis IBD. Therefore, development alternative therapeutic strategies positive efficacy reduced side effects urgently needed. In recent years, great prosperity nanomedicine promoted by advanced nanomaterials redefining more attractive promising for owing their advantages in physiological stability, bioavailability, targeting sites. this review, firstly basic characteristics healthy intestinal microenvironments are presented. Then, different administration routes nanotherapeutics treatment reviewed. Subsequently, specific focus placed on introduction nanotherapeutic treatments based pathogenesis. Finally, some future challenges perspectives currently developed nanomedicines provided. It believed that above topics will attract researchers from various fields including medicine, biological sciences, materials, chemistry pharmaceutics.

Language: Английский

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ROS/Electro Dual-Reactive Nanogel for Targeting Epileptic Foci to Remodel Aberrant Circuits and Inflammatory Microenvironment

ACS Nano, Journal Year: 2023, Volume and Issue: 17(8), P. 7847 - 7864

Published: April 11, 2023

Medicinal treatment against epilepsy is faced with intractable problems, especially epileptogenesis that cannot be blocked by clinical antiepileptic drugs (AEDs) during the latency of epilepsy. Abnormal circuits neurons interact inflammatory microenvironment glial cells in epileptic foci, resulting recurrent seizures and refractory Herein, we have selected phenytoin (PHT) as a model drug to derive ROS-responsive consuming prodrug, which combined an electro-responsive group (sulfonate sodium, SS) focus-recognizing (α-methyl-l-tryptophan, AMT) form hydrogel nanoparticles (i.e., nanogel). The nanogel will target release PHT response high concentration reactive oxygen species (ROS) microenvironment, inhibit overexcited circuits. Meanwhile, clearance ROS, can also reduce oxidative stress alleviate inflammation. Thus, synergistic regulation lesions achieved. Our expected provide more comprehensive strategy for treatment.

Language: Английский

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