Abnormal ac4C modification in metabolic dysfunction associated steatotic liver cells.

The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear due to the complexity of its etiology. The emerging field of the epitranscriptome has shown significant promise in advancing the understanding of disease pathogenesis and developing new therapeutic approaches. Recent research has demonstrated that N4-acetylcytosine (ac4C), an RNA modification within the epitranscriptome, is implicated in progression of various diseases.

Transepithelial transport of nanoparticles in oral drug delivery: From the perspective of surface and holistic property modulation.

Despite the promising prospects of nanoparticles in oral drug delivery, the process of oral administration involves a complex transportation pathway that includes cellular uptake, intracellular trafficking, and exocytosis by intestinal epithelial cells, which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic effects. Current researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells, including surface properties such as ligand modification, surface charge, hydrophilicity/hydrophobicity, intestinal protein corona formation, as well as holistic properties like particle size, shape, and rigidity. Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery systems.

Tea-derived exosome-like nanoparticles prevent irritable bowel syndrome induced by water avoidance stress in rat model.

Background And Aim: Exosome-like nanoparticles (ELNs) have emerged as crucial mediators of intercellular communication, evaluated as potential bioactive nutraceutical biomolecules. We hypothesized that oral ELNs have some therapeutic effect on irritable bowel syndrome (IBS).

Methods: In our study, ELNs from tea (Camellia sinensis) leaves were extracted by differential centrifugation.

Airway epithelial-targeted nanoparticle reverses asthma in inhalation therapy.

Despite extensive research on corticosteroids for treating asthma, their short residence time in the lungs has limited their therapeutic effects in vivo. Nanoparticles have been widely investigated for inhaled drug delivery due to their potential benefits in prolonging drugs' residence time in the lungs. However, the retention of nanoparticles may be limited by mucus and ciliated epithelium clearance mechanisms in the airway.

Cell or cell derivative-laden hydrogels for myocardial infarction therapy: from the perspective of cell types.

Myocardial infarction (MI) is a global cardiovascular disease with high mortality and morbidity. To treat acute MI, various therapeutic approaches have been developed, including cells, extracellular vesicles, and biomimetic nanoparticles. However, the clinical application of these therapies is limited due to low cell viability, inadequate targetability, and rapid elimination from cardiac sites.

Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract.

Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology.

Immune checkpoint blockade (ICB) has gained unparalleled success in the treatment of colorectal cancer (CRC). However, undesired side effects, unsatisfactory response rates, tumor metastasis, and drug resistance still hinder the further application of ICB therapy against CRC. Advancing ICB with nanotechnology can be game-changing.

[Construction of Oral Insulin-Loaded Solid Lipid Nanoparticles and Their Intestinal Epithelial Cell Transcytosis Study].

Objective: To construct solid lipid nanoparticle (SNPs) drug delivery system loaded with peptide and protein drugs by using mixedsolvents, to study the transcytosis mechanisms of SNPs across intestinal epithelial cells, and to improve the endocytosis and transcytosis efficiency of peptide and protein drugs.

Methods: The formulation of insulin-loaded water-in-oil-in-water solid lipid nanoparticles (INS-SNPs) was prepared by using a methanol-chloroform mixed solvent. The formulation was optimized with the single factor screening method.

Complying with the physiological functions of Golgi apparatus for secretory exocytosis facilitated oral absorption of protein drugs.

Intestinal epithelial cells are the primary biological barriers for orally administrated nano-formulations and the delivered protein drugs. Thereinto, besides the cellular uptake, intracellular trafficking pathway and the related exocytosis are of great importance to the trans-epithelial transport of drug-loaded NPs. Herein, inspired by the physiological functions of Golgi apparatus for secreting proteins out of cells, Golgi localization-related amino acid l-cysteine (Cys) was modified on the surface of NPs to see whether and how this modification could guide the Golgi pathway-related transport and facilitate the exocytosis of drug-loaded NPs.

Tailored elasticity combined with biomimetic surface promotes nanoparticle transcytosis to overcome mucosal epithelial barrier.

Overcoming epithelial barriers to enhance drug absorption is a major challenge for nanoparticle (NP)-based mucosal delivery systems. With adequate physicochemical properties, the transepithelial delivery of NPs may be efficiently enhanced. However, little is known about the role of elasticity on the transport of NPs across the polarized epithelium, especially the processes and mechanisms of endocytosis, intracellular trafficking and exocytosis.

Nanoparticles with surface features of dendritic oligopeptides as potential oral drug delivery systems.

Surface features are key to the transcellular transport of nanoparticles (NPs) across intestinal epithelium cells. Endowing the NPs with specific surface features adapted to the physiological conditions of the gastrointestinal (GI) tract holds great potential for the oral delivery of peptide/protein drugs. Therefore, in this work, a glutamic acid conjugated amphiphilic dendrimer (Glu-APD) was synthesized to replace the widely used 1,2-distearoyl-sn-glycero-3-phosphatidyl-ethanolamine-polyethylene glycol (DSPE-PEG) in the preparation of poly(lactic-co-glycolic acid) (PLGA)-based NPs.

Multifunctional Nanoparticles Enable Efficient Oral Delivery of Biomacromolecules via Improving Payload Stability and Regulating the Transcytosis Pathway.

In oral delivery of biomacromolecules, ligand-modified nanoparticles (NPs) have emerged as a promising tool to improve the epithelial uptake of the loaded protein/peptide. Unfortunately, the stability and the transport mechanisms of the biotherapeutics during the intracellular transportation still remained unclear, leading to the poor transepithelial efficiency. Additionally, developing novel approaches to simultaneously monitor the payload bioactivity during the transport processes is veritably benefit for keeping their bioactivity.

Biomimetic Viruslike and Charge Reversible Nanoparticles to Sequentially Overcome Mucus and Epithelial Barriers for Oral Insulin Delivery.

Nanoparticles (NPs) for oral delivery of peptide/protein drugs are largely limited due to the coexistence of intestinal mucus and epithelial barriers. Sequentially overcoming these two barriers is intractable for a single nanovehicle due to the requirements of different or even contradictory surface properties of NPs. To solve this dilemma, a mucus-penetrating virus-inspired biomimetic NP with charge reversal ability (P-R8-Pho NPs) was developed by densely coating poly(lactic- co-glycolic acid) NPs with cationic octa-arginine (R8) peptide and specific anionic phosphoserine (Pho).

Novel Solid Lipid Nanoparticle with Endosomal Escape Function for Oral Delivery of Insulin.

Although nanoparticles (NPs) have been demonstrated as promising tools for improving oral absorption of biotherapeutics, most of them still have very limited oral bioavailability. Lyso-endosomal degradation in epithelial cells is one of the important but often-neglected physiological barriers, limiting the transport of cargoes across the intestinal epithelium. We herein reported a solid lipid nanoparticle (SLN) platform with a unique feature of endosomal escape for oral protein drug delivery.

The combination of endolysosomal escape and basolateral stimulation to overcome the difficulties of "easy uptake hard transcytosis" of ligand-modified nanoparticles in oral drug delivery.

Ligand-modified nanoparticles (NPs) are an effective tool to increase the endocytosis efficiency of drugs, but these functionalized NPs face the drawback of "easy uptake hard transcytosis" in the oral delivery of proteins and peptides. Adversely, the resulting deficiency in transcytosis has not attracted much attention. Herein, NPs modified with the low-density lipoprotein receptor (LDLR) ligand NH-C6-[cMPRLRGC]c-NH, i.

Enhanced Oral Delivery of Protein Drugs Using Zwitterion-Functionalized Nanoparticles to Overcome both the Diffusion and Absorption Barriers.

Oral delivery of protein drugs based on nanoparticulate delivery system requires permeation of the nanoparticles through the mucus layer and subsequent absorption via epithelial cells. However, overcoming these two barriers requires very different or even contradictory surface properties of the nanocarriers, which greatly limits the oral bioavailability of macromolecular drugs. Here we report a simple zwitterions-based nanoparticle (NP) delivery platform, which showed a great potency in simultaneously overcoming both the mucus and epithelium barriers.