title: Internalization and biodistribution of polymersomes into oral squamous cell carcinoma cells in vitro and in vivo.
abstract: The prognosis for oral squamous cell carcinoma (OSCC) is not improving despite advances in surgical treatment. As with many cancers, there is a need to deliver therapeutic agents with greater efficiency into OSCC to improve treatment and patient outcome. The development of polymersomes offers a novel way to deliver therapy directly into tumor cells. Here we examined the internalization and biodistribution of two different fluorescently labeled polymersome formulations; polyethylene oxide (PEO)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) and poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-PDPA, into SCC4 OSCC cells in vitro and in vivo. In vitro SCC4 monolayers internalized PMPC-PDPA and PEO-PDPA at similar rates. However, in vivo PMPC-PDPA polymersomes penetrated deeper and were more widely dispersed in SCC4 tumors than PEO-PDPA polymersomes. In the liver and spleen PMPC-PDPA mainly accumulated in tissue macrophages. However, in tumors PMPC-PDPA was found extensively in the nucleus and cytoplasm of tumor cells as well as in tumor-associated macrophages. Use of PMPC-PDPA polymersomes may enhance polymersome-mediated antitumor therapy.
authors.affiliation: School of Clinical Dentistry, Unit of Oral & Maxillofacial Medicine & Surgery, University of Sheffield, Sheffield, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Murdoch
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Reeves
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hearnden
authors.forename: Helen
authors.initials: H
authors.lastname: Colley
authors.forename: Marzia
authors.initials: M
authors.lastname: Massignani
authors.forename: Irene
authors.initials: I
authors.lastname: Canton
authors.forename: Jeppe
authors.initials: J
authors.lastname: Madsen
authors.forename: Adam
authors.initials: A
authors.lastname: Blanazs
authors.forename: Steve P
authors.initials: SP
authors.lastname: Armes
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.forename: Sheila
authors.initials: S
authors.lastname: Macneil
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Martin H
authors.initials: MH
authors.lastname: Thornhill
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D011108:Polymers / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D011108:Polymers