Dataset Information

Polyethylenimine-Poly(lactic-co-glycolic acid)₂ Nanoparticles Show an Innate Targeting Ability to the Submandibular Salivary Gland via the Muscarinic 3 Receptor.

ABSTRACT: Polymeric nanoparticles have been extensively explored for biomedical applications, especially as framework materials for the construction of functional nanostructures. However, less attention has been paid to the inherent biological activities of those polymers. In this work, one of the commonly used polymers in gene and protein delivery, polyethylenimine-poly(lactic-co-glycolic acid)₂ (PEI-PLGA), was discovered by accident to be able to mediate the nanoparticles to target the submandibular salivary glands of mice after intravenous injection. PEI-PLGA nanoparticles with an unmodified PEI surface selectively accumulated in submandibular salivary glands with ex vivo and in vitro study, suggesting that a ligand-receptor interaction between PEI and muscarinic acetylcholine receptor subtype 3 (M3 receptor) contributed to this affinity. Docking computation for the molecular binding mode between PEI segments and M3 receptor indicated the way they interacted was similar to that of the FDA-approved specific M3 receptor antagonist, tiotropium. The key amino acids mediated this specific interaction between PEI-PLGA nanoparticles and M3 receptor were identified via a simulated alanine mutation study. This work demonstrates the unique characteristic of PEI-PLGA nanoparticles, which may be useful for the development of muscarinic receptor targeted nanomedicines and should be taken into consideration when PEI-based nanoparticles are applied in gene delivery.

SUBMITTER: Xu J

PROVIDER: S-EPMC8614106 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polyethylenimine-Poly(lactic-co-glycolic acid)2 Nanoparticles Show an Innate Targeting Ability to the Submandibular Salivary Gland via the Muscarinic 3 Receptor.

Xu Junchao J Wan Kaiwei K Wang Hui H Shi Xinghua X Wang Jing J Zhong Yi Y Gao Chao C Zhang Yinlong Y Nie Guangjun G

ACS central science 20211104 11

Polymeric nanoparticles have been extensively explored for biomedical applications, especially as framework materials for the construction of functional nanostructures. However, less attention has been paid to the inherent biological activities of those polymers. In this work, one of the commonly used polymers in gene and protein delivery, polyethylenimine-poly(lactic-co-glycolic acid)2 (PEI-PLGA), was discovered by accident to be able to mediate the nanoparticles to target the ...[more]

PMID: 34841064

Similar Datasets

Project description:BackgroundOrgan replacement regenerative therapy based on human adult stem cells may be effective for salivary gland hypofunction. However, the generated tissues are immature because the signaling factors that induce the differentiation of human salivary gland stem cells into salivary glands are unknown.MethodsIsolated human submandibular gland stem/progenitor cells (hSMGepiS/PCs) were characterized and three-dimensionally (3D) cultured to generate organoids and further induced by fibroblast growth factor 10 (FGF10) in vitro. The induced spheres alone or in combination with embryonic day 12.5 (E12.5) mouse salivary gland mesenchyme were transplanted into the renal capsules of nude mice to assess their development in vivo. Immunofluorescence, quantitative reverse transcriptase-polymerase chain reaction, calcium release analysis, western blotting, hematoxylin-eosin staining, Alcian blue-periodic acid-Schiff staining, and Masson's trichrome staining were performed to assess the structure and function of generated tissues in vitro and in vivo.ResultsThe isolated hSMGepiS/PCs could be long-term cultured with a stable genome. The organoids treated with FGF10 [FGF10 (+) group] exhibited higher expression of salivary gland-specific markers; showed spatial arrangement of AQP5+, K19+, and SMA+ cells; and were more sensitive to the stimulation by neurotransmitters than untreated organoids [FGF10 (-) group]. After heterotopic transplantation, the induced cell spheres combined with mouse embryonic salivary gland mesenchyme showed characteristics of mature salivary glands, including a natural morphology and saliva secretion.ConclusionFGF10 promoted the development of the hSMGepiS/PC-derived salivary gland organoids by the expression of differentiation markers, structure formation, and response to neurotransmitters in vitro. Moreover, the hSMGepiS/PCs responded to the niche in mouse embryonic mesenchyme and further differentiated into salivary gland tissues with mature characteristics. Our study provides a foundation for the regenerative therapy of salivary gland diseases.

Project description:Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix) adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft progression was determined as follows: cleft cell contractility, cleft region cell-cell adhesion strength, epithelial cell mitosis rate, and cell-matrix adhesion strength.

Dataset Information

Polyethylenimine-Poly(lactic-co-glycolic acid)₂ Nanoparticles Show an Innate Targeting Ability to the Submandibular Salivary Gland via the Muscarinic 3 Receptor.

Publications

Polyethylenimine-Poly(lactic-<i>co</i>-glycolic acid)<sub>2</sub> Nanoparticles Show an Innate Targeting Ability to the Submandibular Salivary Gland via the Muscarinic 3 Receptor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets