ABSTRACT
Acute lung injury (ALI) is a prevalent and critical condition in clinical practice. Although certain pharmacological interventions have demonstrated benefits in preclinical studies, none have been proven entirely effective thus far. Therefore, the development of more efficient treatment strategies for ALI is imperative. In this study, we prepared nanostructured lipid carriers (NLCs) conjugated with anti-VCAM-1 antibodies to encapsulate melatonin (MLT), resulting in VCAM/MLT NLCs. This approach aimed to enhance the distribution of melatonin in lung vascular endothelial cells. The VCAM/MLT NLCs had an average diameter of 364 nm, high drug loading content, and a sustained drug release profile. Notably, the NLCs conjugated with anti-VCAM-1 antibodies demonstrated more specific cellular delivery mediated by the VCAM-1 receptors, increased cellular internalization, and enhanced accumulation in lung tissues. Treatment with VCAM/MLT NLCs effectively alleviated pulmonary inflammation by activating NLRP3 inflammasome-dependent pyroptosis through up-regulation of Sirtuin 1. Our findings suggest that VCAM/MLT NLCs demonstrate remarkable therapeutic effects on ALI in both in vitro and in vivo settings, making them a promising and efficient treatment strategy for ALI.
Subject(s)
Acute Lung Injury , Melatonin , Nanostructures , Vascular Cell Adhesion Molecule-1 , Animals , Humans , Male , Mice , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Drug Carriers/chemistry , Inflammasomes/metabolism , Lipids/chemistry , Melatonin/pharmacology , Melatonin/administration & dosage , Nanostructures/chemistry , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/drug effects , Signal Transduction/drug effects , Sirtuin 1/metabolism , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
[This corrects the article DOI: 10.3389/fbioe.2022.984424.].
ABSTRACT
Ischemic stroke is the most common type of cerebrovascular disease with high disability rate and mortality. The blood-brain barrier (BBB) protects the homeostasis of the brain's microenvironment and impedes the penetration of 98% of drugs. Therefore, effective treatment requires the better drug transport across membranes and increased drug distribution. Nanoparticles are a good choice for drugs to cross BBB. The main pathways of nano delivery systems through BBB include passive diffusion, adsorption-mediated endocytosis, receptor-mediated transport, carrier-mediated transport, etc. At present, the materials used in brain-targeted delivery can be divided into natural polymer, synthetic polymers, inorganic materials and phospholipid. In this review, we first introduced several ways of nano delivery systems crossing the BBB, and then summarized their applications in ischemic stroke. Based on their potential and challenges in the treatment of ischemic stroke, new ideas and prospects are proposed for designing feasible and effective nano delivery systems.
ABSTRACT
[This corrects the article DOI: 10.1021/acsmedchemlett.1c00585.].
ABSTRACT
Pulmonary vascular endothelial cells (VECs) are the main damaged cells in the pathogenesis of various respiratory diseases and they mediate the development and regulation of the diseases. Effective intervention targeting pulmonary VECs is of great significance for the treatment of respiratory diseases. A variety of cell markers are expressed on the surface of VECs, some of which can be specifically combined with the drugs or carriers modified by corresponding ligands such as ICAM-1, PECAM-1, and P-selectin, to achieve effective delivery of drugs in lung tissues. In addition, the great endothelial surface area of the pulmonary vessels, the "first pass effect" of venous blood in lung tissues, and the high volume and relatively slow blood perfusion rate of pulmonary capillaries further promote the drug distribution in lung tissues. This review summarizes the representative markers at the onset of respiratory diseases, drug delivery systems designed to target these markers and their therapeutic effects.
ABSTRACT
Based on the pathological mechanisms of acute kidney injury (AKI), a stepwise targeting curcumin derivative, Ser@TPP@CUR, was developed in this study. Ser@TPP@CUR can be specifically internalized by renal tubular epithelial cells via KIM-1 receptor-mediated endocytosis and then actively distributed in mitochondria under the effect of TPP, a mitochondrial targeting molecule. Both in vitro and in vivo results showed that Ser@TPP@CUR effectively ameliorated injured renal tubular epithelial cells and improved renal functions of AKI mice.
