Unlocking the promise of mRNA therapeutics

Nature Biotechnology, Год журнала: 2022, Номер 40(11), С. 1586 - 1600

Опубликована: Ноя. 1, 2022

Язык: Английский

---

Biomimetic Design of Mitochondria‐Targeted Hybrid Nanozymes as Superoxide Scavengers

Advanced Materials, Год журнала: 2021, Номер 33(9)

Опубликована: Янв. 22, 2021

Development of enzyme mimics for the scavenging excessive mitochondrial superoxide (O2•- ) can serve as an effective strategy in treatment many diseases. Here, protein reconstruction technology and nanotechnology is taken advantage to biomimetically create artificial hybrid nanozyme. These nanozymes consist ferritin-heavy-chain-based scaffold a metal nanoparticle core active center. This cascade nanozyme possesses dismutase- catalase-like activities also targets mitochondria by overcoming multiple biological barriers. Using cardiac ischemia-reperfusion animal models, protective advantages are demonstrated vivo during oxidative injury recovery heart functionality following infarction via systemic delivery localized release from adhesive hydrogels (i.e., patch), respectively. study illustrates de novo design development provides promising therapeutic option alleviating damage regenerative medicine.

Язык: Английский

---

Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and Their Delivery Strategies

Advanced Healthcare Materials, Год журнала: 2021, Номер 10(7)

Опубликована: Янв. 12, 2021

Abstract Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion angiogenesis, reduction in fibrosis. This review focuses on profiling the effects paracrine signals MSCs, commonly referred secretome, highlighting various engineering approaches tune MSC secretome. Recent advances biomaterials‐based therapeutic strategies delivery MSCs MSC‐derived secretome form extracellular vesicles are discussed, along with advantages challenges.

Язык: Английский

---

M2 Macrophage‐Derived sEV Regulate Pro‐Inflammatory CCR2⁺ Macrophage Subpopulations to Favor Post‐AMI Cardiac Repair

Advanced Science, Год журнала: 2023, Номер 10(14)

Опубликована: Март 22, 2023

Abstract Tissue‐resident cardiac macrophage subsets mediate tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)‐expressing macrophages have phenotypical similarities to M1‐polarized macrophages, are pro‐inflammatory, recruit CCR2 + circulating monocytes infarcted myocardium. Small extracellular vesicles (sEV) from ̶ which phenotypically resemble M2‐polarized promote anti‐inflammatory activity repair. Here, the authors harvested M2 macrophage‐derived sEV (M2 EV ) bone‐marrow‐derived for intramyocardial injection recapitulation of sEV‐mediated in ischemic‐reperfusion (I/R) injured hearts. Rats pigs received sham surgery; I/R without treatment; or with autologous treatment. rescued function attenuated injury markers, infarct size, scar size. inhibited numbers, reduced monocyte‐derived recruitment sites, induced M1‐to‐M2 switching promoted neovascularization. Analysis microRNA content revealed abundant miR‐181b‐5p, regulated glucose uptake, glycolysis, mitigated mitochondrial reactive oxygen species generation. Functional blockade miR‐181b‐5p is detrimental beneficial actions resulted failure inhibit numbers Taken together, this investigation showed that function, improved repair, via miR‐181b‐5p‐dependent mechanisms, indicating an option cell‐free therapy AMI.

Язык: Английский

---

Protein Coronas Derived from Mucus Act as Both Spear and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular Transport in Enterocytes

ACS Nano, Год журнала: 2024, Номер 18(10), С. 7455 - 7472

Опубликована: Фев. 28, 2024

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy diminished the formation of protein coronas (PCs) when they interact with matrices. PCs are broadly implicated in affecting fate NPs vivo vitro, yet few studies have investigated formed during interactions mucosa, especially mucus. In study, we constructed transferrin modified (Tf-NPs) as model explored mechanisms effects that had subsequent impact transcellular transport Tf-NPs. mucus-secreting cells, Tf-NPs adsorbed more proteins from mucus layers, which masked, displaced, dampened active targeting Tf-NPs, thereby weakening endocytosis efficiencies. mucus-free intracellular trafficking, enhanced transcytosis related functions. Inspired soft artificial biomimetic membranes, used mucin an "active PC" to precoat (M@Tf-NPs), limited negative impacts "passive PCs" interface improved favorable routes endocytosis. M@Tf-NPs associated endoplasmic reticulum-Golgi functions, prompting exocytosis. summary, shielded against absorption also could be employed spear break through barrier. These findings offer theoretical foundation design platform enhance efficiency oral-administered nanomedicines.

Язык: Английский

---

Biomimetic Design of Artificial Hybrid Nanocells for Boosted Vascular Regeneration in Ischemic Tissues

Advanced Materials, Год журнала: 2022, Номер 34(14)

Опубликована: Фев. 2, 2022

Restoration of sufficient blood supply for the treatment ischemia remains a significant scientific and clinical challenge. Here, cell-like nanoparticle delivery technology is introduced that capable recapitulating multiple cell functions spatiotemporal triggering vascular regeneration. Specifically, copper-containing protein successfully prepared using recombinant scaffold based on de novo design strategy, which facilitates timely release nitric oxide improved accumulation particles within ischemic tissues. Through closely mimicking physiological cues, authors demonstrate benefits bioactive factors secreted from hypoxic stem cells promoting angiogenesis. Following this cell-mimicking manner, artificial hybrid nanosized (Hynocell) are constructed by integrating secretome into nanoparticles with surface coatings membranes fused protein. The Hynocell, hybridized different cell-derived components, provides synergistic effects targeting tissues regeneration in acute hindlimb myocardial infarction models. This study offers new insights utilization nanotechnology to potentiate development cell-free therapeutics.

Язык: Английский

---

Tumor Cell Nanovaccines Based on Genetically Engineered Antibody‐Anchored Membrane

Advanced Materials, Год журнала: 2023, Номер 35(13)

Опубликована: Янв. 30, 2023

Abstract Despite the promise in whole‐tumor cell vaccines, a key challenge is to overcome lack of costimulatory signals. Here, agonistic‐antibody‐boosted tumor nanovaccines are reported by genetically engineered antibody‐anchored membrane (AAM) technology, capable effectively activating pathways. Specifically, AAM can be stably constructed following genetic engineering membranes with anti‐CD40 single chain variable fragment (scFv), an agonistic antibody induce The versatilely designed and obtained based on scFv‐anchored nanotechnology. Following vaccination, nanovaccine (Nano‐AAM/CD40) significantly facilitates dendritic maturation CD40‐humanized transgenic mice subsequent adaptive immune responses. Compared membrane‐based alone, enhanced antitumor efficacy both “hot” “cold” models Nano‐AAM/CD40 demonstrates importance antibodies development tumor‐cell‐based vaccines. To expand design nanovaccines, further incorporation lysates into conceptually construct cell‐like results boosted responses improved against malignant tumors inoculated mice. Overall, this technology provides versatile components checkpoints.

Язык: Английский

---

Cyclosporine A-loaded apoferritin alleviates myocardial ischemia-reperfusion injury by simultaneously blocking ferroptosis and apoptosis of cardiomyocytes

Acta Biomaterialia, Год журнала: 2023, Номер 160, С. 265 - 280

Опубликована: Фев. 21, 2023

Язык: Английский

---

Highly efficient fabrication of functional hepatocyte spheroids by a magnetic system for the rescue of acute liver failure

Biomaterials, Год журнала: 2023, Номер 294, С. 122014 - 122014

Опубликована: Янв. 20, 2023

Язык: Английский

---

Minimally invasive snakebite inspired microneedle delivery system for internal organs

Bioactive Materials, Год журнала: 2025, Номер 49, С. 576 - 585

Опубликована: Март 24, 2025

Язык: Английский

---