Internalization and biodistribution of polymersomes into oral squamous cell carcinoma cells in vitro and in vivo.
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.
Murdoch
Craig
C
School of Clinical Dentistry, Unit of Oral & Maxillofacial Medicine & Surgery, University of Sheffield, Sheffield, UK.
Reeves
Kim J
KJ
Hearnden
Vanessa
V
Colley
Helen
H
Massignani
Marzia
M
Canton
Irene
I
Madsen
Jeppe
J
Blanazs
Adam
A
Armes
Steve P
SP
Lewis
Andrew L
AL
Macneil
Sheila
S
Brown
Nicola J
NJ
Thornhill
Martin H
MH
Battaglia
Giuseppe
G
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
D011108:Polymers