Background: The mechanisms underlying postoperative atrial fibrillation (POAF) remain unclear.
Objectives: The aim of this study was to test the hypothesis that targeted chemical ganglionated plexi (GP) modulation of all major left atrial-pulmonary vein GP using novel nanoformulated calcium chloride (nCaCl) can reverse postoperative neuroelectrical remodeling by suppressing vagosympathetic nerve activity and the localized inflammatory process, both critical substrates of POAF.
Methods: In a novel canine model of POAF with serial thoracopericardiotomies, sympathetic nerve activity (SNA), vagal nerve activity (VNA) and GP nerve activity (GPNA) were recorded; spontaneous and in vivo AF vulnerability were assessed; and atrial and circulating inflammatory markers and norepinephrine (NE) were measured to determine the neuroelectrical remodeling that promotes POAF and its subsequent modulation with nCaCl GP treatment (n = 6) vs saline sham controls (n = 6).
Idiopathic pulmonary fibrosis (IPF) is a lethal disorder characterized by relentless progression of lung fibrosis that causes respiratory failure and early death. Currently, no curative treatments are available, and existing therapies include a limited selection of antifibrotic agents that only slow disease progression. The development of novel therapeutics has been hindered by a limited understanding of the disease's etiology and pathogenesis.
View Article and Find Full Text PDFCancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8--methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand.
View Article and Find Full Text PDFStimuli-responsive peptides, particularly pH-responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH-responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH-responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non-natural amino acids featuring chemically diverse tertiary amine side chains.
View Article and Find Full Text PDFTo develop an inhalable drug delivery system, we synthesized poly (lactic--glycolic acid) nanoparticles with Remdesivir (RDV NPs) as an antiviral agent against SARS-CoV-2 replication and formulated Remdesivir-loaded nanocomposites (RDV NCs) coating of RDV NPs with novel supramolecular cell-penetrating peptide nanofibers (NFs) to enhance cellular uptake and intracellular drug delivery. RDV NPs and RDV NCs were characterized using variou techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and fluorescent microscopy. The cytotoxicity of RDV NCs was assessed in Vero E6 cells and primary human lung epithelial cells, with no significant cytotoxicity observed up to 1000 μg mL and 48 h.
View Article and Find Full Text PDFPeptide-based hydrogels have gained considerable attention as a compelling platform for various biomedical applications in recent years. Their attractiveness stems from their ability to seamlessly integrate diverse properties, such as biocompatibility, biodegradability, easily adjustable hydrophilicity/hydrophobicity, and other functionalities. However, a significant drawback is that most of the functional self-assembling peptides cannot form robust hydrogels suitable for biological applications.
View Article and Find Full Text PDFCell membrane-derived nanoparticles (NPs) have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells, impeding systemic clearance, and altering foreign body responses. Besides NP technology, adoptive immunotherapy has emerged due to its promise in cancer specificity and therapeutic efficacy. In this research, we developed a biomimetic drug carrier based on chimeric antigen receptor (CAR) transduced T-cell membranes.
View Article and Find Full Text PDFTo develop a potential cancer treatment, we formulated a novel drug delivery platform made of poly(lactic-co-glycolic) acid (PLGA) and used a combination of an emerging siRNA technology and an extracted natural substance called catechins. The synthesized materials were characterized to determine their properties, including morphology, hydrodynamic size, charge, particle stability, and drug release profile. The therapeutic effect of -siRNA and epigallocatechin gallate (EGCG) was revealed to have remarkable cytotoxicity towards HepG2 when in soluble formulation.
View Article and Find Full Text PDFNear-infrared fluorescence imaging has emerged as a noninvasive, inexpensive, and ionizing-radiation-free monitoring tool for assessing tumor growth and treatment efficacy. In particular, ultrasound switchable fluorescence (USF) imaging has been explored with improved imaging sensitivity and spatial resolution in centimeter-deep tissues. This study achieved size control of polymer-based and indocyanine green (ICG) encapsulated USF contrast agents, capable of accumulating at the tumor after intravenous injections.
View Article and Find Full Text PDFBiomed Opt Express
September 2023
Measuring the local background temperature in diseased and inflamed tissues is highly desirable, especially in a non-invasive way. In this work, ultrasound-switchable fluorescence (USF) technique was utilized to estimate the local background temperature for the first time by analyzing the temperature dependence of fluorescence emission from USF contrast agents induced by a focused ultrasound (FU) beam. First, temperature-sensitive USF agents with distinct temperature switching-on thresholds were synthesized, and their thermal switching characteristics were quantified using an independent spectrometer system.
View Article and Find Full Text PDFBacterial infection has traditionally been treated with antibiotics, but their overuse is leading to the development of antibiotic resistance. This may be mitigated by alternative approaches to prevent or treat bacterial infections without utilization of antibiotics. Among the alternatives is the use of photo-responsive antimicrobial nanoparticles and/or nanocomposites, which present unique properties activated by light.
View Article and Find Full Text PDFClinical resistance towards treatment is a major concern in cancer therapy. This is due to in vitro studies lacking essential microenvironmental aspects. Tumor-hypoxia is an important pathophysiological phenomenon in numerous malignant tumors.
View Article and Find Full Text PDFPercutaneous coronary intervention (PCI) is a common procedure for the management of coronary artery obstruction. However, it usually causes vascular wall injury leading to restenosis that limits the long-term success of the PCI endeavor. The ultimate objective of this study was to develop the targeting nanoparticles (NPs) that were destined for the injured subendothelium and attract endothelial progenitor cells (EPCs) to the damaged location for endothelium regeneration.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2022
Effective drug delivery to pulmonary sites will benefit from the design and synthesis of novel drug delivery systems that can overcome various tissue and cellular barriers. Cell penetrating peptides (CPPs) have shown promise for intracellular delivery of various imaging probes and therapeutics. Although CPPs improve delivery efficacy to a certain extent, they still lack the scope of engineering to improve the payload capacity and protect the payload from the physiological environment in drug delivery applications.
View Article and Find Full Text PDFAngiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose.
View Article and Find Full Text PDFResearchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups.
View Article and Find Full Text PDFSelf-assembled peptides are an emerging family of biomaterials that show great promise for a range of biomedical and biotechnological applications. Introducing and tuning the pH-responsiveness of the assembly is highly desirable for improving their biological activities. Inspired by proteins with internal ionizable residues, we report a simple but effective approach to constructing pH-responsive peptide assembly containing unnatural ionic amino acids with an aliphatic tertiary amine side chain.
View Article and Find Full Text PDFWiley Interdiscip Rev Nanomed Nanobiotechnol
January 2023
Recently, the aging population has increased exponentially around the globe bringing more challenges to improve quality of life in those populations while reducing the economic burden on healthcare systems. Aging is associated with changes in the immune system culminating in detrimental effects such as immune dysfunction, immunosenescence, and chronic inflammation. Age-related decline of immune functions is associated with various pathologies including cardiovascular, autoimmune, neurodegenerative, and infectious diseases to name a few.
View Article and Find Full Text PDFLung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor targeting nanoparticles that can provide cancer specific therapies. In this research, we have developed novel dual-stimuli nanoparticles (E-DSNPs), comprised of two parts; (1) Core: responsive to glutathione as stimuli and encapsulating Cisplatin (a chemo-drug), and (2) Shell: responsive to irradiation as stimuli and containing NU7441 (a radiation sensitizer).
View Article and Find Full Text PDFCardiac extracellular matrices (ECM) play crucial functional roles in cardiac biomechanics. Previous studies have mainly focused on collagen, the major structural ECM in heart wall. The role of elastin in cardiac mechanics, however, is poorly understood.
View Article and Find Full Text PDFPurpose: The development of two novel pH-only and pH- and thermo-responsive theranostic nanoparticle (NP) formulations to deliver an anticancer drug and track the accumulation and therapeutic efficacy of the formulations through inherent fluorescence.
Methods: A pH-responsive formulation was synthesized from biodegradable photoluminescent polymer (BPLP) and sodium bicarbonate (SBC) via an emulsion technique, while a thermoresponsive BPLP copolymer (TFP) and SBC were used to synthesize a dual-stimuli responsive formulation via free radical co-polymerization. Cisplatin was employed as a model drug and encapsulated during synthesis.
Bioadhesives are intended to facilitate the fast and efficient reconnection of tissues to restore their functionality after surgery or injury. The use of mussel-inspired hydrogel systems containing pendant catechol moieties is promising for tissue attachment under wet conditions. However, the adhesion strength is not yet ideal.
View Article and Find Full Text PDFIn the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpose of the current study was to deliver a Notch Intracellular Domain (NICD)-encoded plasmid poly(lactic--glycolic acid) (PLGA) nanoparticles and to investigate the toxic environmental side effects for an experiment.
View Article and Find Full Text PDFLocal skin cancer recurrence occurs in ∼12% of the patients post-surgery due to persistent growth of residual cancer cells. Wound infection is another significant complication following surgery. We report a novel -forming nanocomposite hydrogel (NCH) containing PLGA-carboxymethyl chitosan nanoparticles (186 nm) for localized pH-responsive skin cancer therapy and wound healing.
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