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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 triblock-copolymer, poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PMOXA\u2013PDMS\u2013PMOXA), 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\u2013PDMS\u2013PMOXA polymersomes were used to visualize them inside cells. N-Methyl-d-aspartate receptor (NMDAR) 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\u2013vis fluorescence spectroscopy, and asymmetrical flow field-flow fractionation (AF4). 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 antagonist-functionalized polymersomes targeted selectively neurons over glial 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.<\/jats:p>","DOI":"10.1021\/acsomega.8b02311","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T15:41:55Z","timestamp":1540309315000},"page":"13882-13893","source":"Crossref","is-referenced-by-count":43,"title":["Encapsulation and Delivery of Neutrophic Proteins\nand Hydrophobic Agents Using PMOXA\u2013PDMS\u2013PMOXA Triblock\nPolymersomes"],"prefix":"10.1021","volume":"3","author":[{"given":"Alexandre","family":"Moquin","sequence":"first","affiliation":[{"name":"McGill University , , 3655 Promenade Sir-William-Osler , , ,","place":["Montreal, Que\u0301bec, Canada, H3G 1Y6"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Ji","sequence":"additional","affiliation":[{"name":"McGill University , , 3655 Promenade Sir-William-Osler , , ,","place":["Montreal, Que\u0301bec, Canada, H3G 1Y6"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Neibert","sequence":"additional","affiliation":[{"name":"McGill University , , 3655 Promenade Sir-William-Osler , , ,","place":["Montreal, Que\u0301bec, Canada, H3G 1Y6"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5844-6687","authenticated-orcid":true,"given":"Franc\u0327oise M.","family":"Winnik","sequence":"additional","affiliation":[{"name":"Universite\u0301 de Montre\u0301al , , CP 6128 Succursale Centre-Ville , , ,","place":["Montre\u0301al, Que\u0301bec, Canada, H3C 3J7"]},{"name":"National Institute for Materials Science (NIMS) , , 1-1 Namiki , , ,","place":["Tsukuba, Ibaraki, Japan, 305-0044"]},{"name":"University of Helsinki , , ,","place":["Helsinki, Finland, FI-00014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0017-5201","authenticated-orcid":true,"given":"Dusica","family":"Maysinger","sequence":"additional","affiliation":[{"name":"McGill University , , 3655 Promenade Sir-William-Osler , , ,","place":["Montreal, Que\u0301bec, Canada, H3G 1Y6"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,10,23]]},"reference":[{"key":"2026090415093514600_cit1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/imr.12018","article-title":"Compartmentalization of signaling by vesicular trafficking:\na shared building design for the immune synapse and the primary cilium","volume":"251","author":"Finetti","year":"2013","journal-title":"Immunol. 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Neurovirol."},{"key":"2026090415093514600_cit5","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.3233\/jad-132135","article-title":"Proteins recruited\nto exosomes by tau overexpression implicate novel cellular mechanisms\nlinking tau secretion with Alzheimer\u2019s disease","volume":"40","author":"Saman","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"2026090415093514600_cit6","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.3233\/jad-132135","article-title":"Exosomal doxorubicin reduces the cardiac toxicity of\ndoxorubicin","volume":"40","author":"Toffoli","year":"2015","journal-title":"Nanomedicine"},{"key":"2026090415093514600_cit7","doi-asserted-by":"publisher","first-page":"2963","DOI":"10.2217\/nnm.15.118","article-title":"Microvesicle- and exosome-mediated\ndrug delivery enhances the cytotoxicity of Paclitaxel in autologous\nprostate cancer cells","volume":"10","author":"Saari","year":"2015","journal-title":"J. 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Histol."},{"key":"2026090415093514600_cit46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.lfs.2014.08.016","article-title":"Curcumin as\na wound healing agent","volume":"116","author":"Akbik","year":"2014","journal-title":"Life Sci."},{"key":"2026090415093514600_cit47","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.nano.2014.09.004","article-title":"Curcumin-encapsulated nanoparticles\nas innovative antimicrobial\nand wound healing agent","volume":"11","author":"Krausz","year":"2015","journal-title":"Nanomedicine"},{"key":"2026090415093514600_cit48","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.jid.2016.09.039","article-title":"Overexpression\nof CD109 in the Epidermis Differentially Regulates ALK1 Versus ALK5\nSignaling and Modulates Extracellular Matrix Synthesis in the Skin","volume":"137","author":"Vorstenbosch","year":"2017","journal-title":"J. Invest. Dermatol."},{"key":"2026090415093514600_cit49","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1042\/bj20141488","article-title":"Soluble CD109 binds\nTGF- and antagonizes TGF- signalling\nand responses","volume":"473","author":"Li","year":"2016","journal-title":"Biochem. J."},{"key":"2026090415093514600_cit50","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/j.bbamcr.2011.01.028","article-title":"The TGF-\u03b2 co-receptor,\nCD109, promotes internalization and degradation of TGF-\u03b2 receptors","volume":"1813","author":"Bizet","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"2026090415093514600_cit51","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1096\/fj.05-5229fje","article-title":"Identification of CD109 as part of\nthe TGF-\u03b2 receptor system in human keratinocytes","volume":"20","author":"Finnson","year":"2006","journal-title":"Faseb. 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