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.

Keywords::

• biodistribution
• cancer
• drug delivery
• oral squamous cell carcinoma
• PMPC
• polymer
• polymersome
• tumor-associated macrophages

Financial & competing interests disclosure

This study was sponsored by Biocompatibles UK Ltd. Steve P Armes is the recipient of a Royal Society Wolfson Research Merit Award. Craig Murdoch, Helen Colley, Martin H Thornhill and Giuseppe Battaglia acknowledge the support of Yorkshire Cancer Research. Marzia Massignani is sponsored by an ESPRC/White Rose DTC PhD studentship, Vanessa Hearnden is funded by a DTA EPSRC PhD studentship and Kim J Reeves is funded by a European Framework VI programme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval and the UK Home office approval for all animal experiments and followed the principles outlined in the Declaration of Helisinki.

Additional information

Funding

This study was sponsored by Biocompatibles UK Ltd. Steve P Armes is the recipient of a Royal Society Wolfson Research Merit Award. Craig Murdoch, Helen Colley, Martin H Thornhill and Giuseppe Battaglia acknowledge the support of Yorkshire Cancer Research. Marzia Massignani is sponsored by an ESPRC/White Rose DTC PhD studentship, Vanessa Hearnden is funded by a DTA EPSRC PhD studentship and Kim J Reeves is funded by a European Framework VI programme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.