Encapsulation and Delivery of Neutrophic Proteins and Hydrophobic Agents Using PMOXA-PDMS-PMOXA Triblock Polymersomes

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Moquin , A , Ji , J , Neibert , K , Winnik , F M & Maysinger , D 2018 , ' Encapsulation and Delivery of Neutrophic Proteins and Hydrophobic Agents Using PMOXA-PDMS-PMOXA Triblock Polymersomes ' , ACS Omega , vol. 3 , no. 10 , pp. 13882-13893 . https://doi.org/10.1021/acsomega.8b02311

Title: Encapsulation and Delivery of Neutrophic Proteins and Hydrophobic Agents Using PMOXA-PDMS-PMOXA Triblock Polymersomes
Author: Moquin, Alexandre; Ji, Jeff; Neibert, Kevin; Winnik, Francoise M.; Maysinger, Dusica
Contributor: University of Helsinki, Department of Chemistry
Date: 2018-10
Language: eng
Number of pages: 12
Belongs to series: ACS Omega
ISSN: 2470-1343
URI: http://hdl.handle.net/10138/267201
Abstract: Polymersomes are attractive nanocarriers for hydrophilic and lipophilic drugs; they are more stable than liposomes, tunable, and relatively easy to prepare. The copolymer composition and molar mass are critical features that determine the physicochemical properties of the polymersomes including the rate of drug release. We used the triblockcopolymer, poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PIVIOXA-PDIVIS-PMOXA), to form amphipathic polymersomes capable of loading proteins and small hydrophobic agents. The selected agents were unstable neurotrophins (nerve growth factor and brain -derived neurotrophic factor), a large protein CD109, and the fluorescent drug curcumin. We prepared, characterized, and tested polymersomes loaded with selected agents in 2D and 3D biological models. Curcumin-loaded and rhodamine-bound PMOXA-PDMS-PMOXA polymersomes were used to visualize them inside cells. NMethyl-D-aspartate receptor (NNIDAR) agonists and antagonists were also covalently attached to the surface of polymersomes for targeting neurons. Labeled and unlabeled polymersomes with or without loaded agents were characterized using dynamic light scattering (DLS), UV-vis fluorescence spectroscopy, and asymmetrical flow field-flow fractionation (AF(4)). Polymersomes were imaged and tested for biological activity in human and murine fibroblasts, murine macrophages, primary murine dorsal root ganglia, and murine hippocampal cultures. Polymersomes were rapidly internalized and there was a clear intracellular co-localization of the fluorescent drug (curcumin) with the fluorescent rhodamine-labeled polymersomes. Polymersomes containing CD109, a glycosylphosphatidylinositol-anchored protein, promoted cell migration in the model of wound healing. Nerve growth factor-loaded polymersomes effectively enhanced neurite outgrowth in dissociated and explanted dorsal root ganglia. Brain -derived neurotrophic factor increased dendritic spine density in serum-deprived hippocampal slice cultures. NMDAR agonist-and antagomst-functionalized polymersomes targeted selectively neurons over filial cells in mixed cultures. Collectively, the study reveals the successful incorporation into polymersomes of biologically active trophic factors and small hydrophilic agents that retain their biological activity in vitro, as demonstrated in selected central and peripheral tissue models.
Subject: NERVE GROWTH-FACTOR
TRAUMATIC BRAIN-INJURY
SYNAPTIC PLASTICITY
DRUG-DELIVERY
TGF-BETA
CANCER
DOXORUBICIN
COPOLYMER
EXOSOMES
CURCUMIN
116 Chemical sciences
221 Nano-technology
317 Pharmacy
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