Contrast-enhanced MRI-guided photodynamic cancer therapy with a pegylated bifunctional polymer conjugate.
OBJECTIVE
To study contrast-enhanced MRI guided photodynamic therapy with a pegylated bifunctional polymer conjugate containing an MRI contrast agent and a photosensitizer for minimally invasive image-guided cancer treatment.


METHODS
Pegylated and non-pegylated poly-(L-glutamic acid) conjugates containing mesochlorin e6, a photosensitizer, and Gd(III)-DO3A, an MRI contrast agent, were synthesized. The effect of pegylation on the biodistribution and tumor targeting was non-invasively visualized in mice bearing MDA-MB-231 tumor xenografts with MRI. MRI-guided photodynamic therapy was carried out in the tumor bearing mice. Tumor response to photodynamic therapy was evaluated by dynamic contrast enhanced MRI and histological analysis.


RESULTS
The pegylated conjugate had longer blood circulation, lower liver uptake and higher tumor accumulation than the non-pegylated conjugate as shown by MRI. Site-directed laser irradiation of tumors resulted in higher therapeutic efficacy for the pegylated conjugate than the non-pegylated conjugate. Moreover, animals treated with photodynamic therapy showed reduced vascular permeability on DCE-MRI and decreased microvessel density in histological analysis.


CONCLUSIONS
Pegylation of the polymer bifunctional conjugates reduced non-specific liver uptake and increased tumor uptake, resulting in significant tumor contrast enhancement and high therapeutic efficacy. The pegylated poly(L-glutamic acid) bifunctional conjugate is promising for contrast enhanced MRI guided photodynamic therapy in cancer treatment.
Vaidya
Anagha
A
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Sun
Yongen
Y
Feng
Yi
Y
Emerson
Lyska
L
Jeong
Eun-Kee
EK
Lu
Zheng-Rong
ZR
D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers; D005260:Female; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000378:metabolism; D053783:Magnetic Resonance Imaging, Interventional; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008652:Mesoporphyrins / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011099:Polyglutamic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D003287:Contrast Media; D004337:Drug Carriers; D006571:Heterocyclic Compounds; D008652:Mesoporphyrins; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C062402:gadoteridol; C088297:meso-chlorin e(6) monoethylene diamine; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D005682:Gadolinium