Contrast enhanced MRI-guided photodynamic therapy for site-specific cancer treatment.
Photodynamic therapy (PDT) is a minimally invasive and effective approach for cancer treatment. It is potentially useful for treating tumors that are not accessible to surgery, radiation, or destructive ablations, and are resistant to chemotherapy. Efficacious treatment of interstitial tumors with PDT requires efficient delivery of photosensitizers and accurate location of tumor tissues for effective light irradiations. In this study we performed contrast-enhanced (CE) MRI-guided PDT with a bifunctional polymer conjugate containing both a magnetic resonance imaging (MRI) contrast agent and a photosensitizer, poly(L-glutamic acid) (PGA)-(Gd-DO3A)-mesochlorin e(6) (Mce(6)). The efficacy of the bifunctional conjugate in cancer CE-MRI and cancer treatment was evaluated in athymic nude mice bearing MDA-MB-231 human breast carcinoma xenografts, with PGA-(Gd-DO3A) used as a control. The polymer conjugates preferentially accumulated in the solid tumor due to the hyperpermeability of the tumor vasculature, resulting in significant tumor enhancement for accurate tumor detection and localization by MRI. Significant therapeutic response was observed for PDT with the bifunctional conjugate as compared to the control. CE-MRI-guided PDT with the bifunctional conjugate is effective for tumor detection and minimally invasive cancer treatment.
Vaidya
Anagha
A
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah , USA.
Sun
Yongen
Y
Ke
Tianyi
T
Jeong
Eun-Kee
EK
Lu
Zheng-Rong
ZR
D000704:Analysis of Variance; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D003287:Contrast Media / Q000138:chemical synthesis / Q000494:pharmacology; D005240:Feasibility Studies; D053783:Magnetic Resonance Imaging, Interventional; D008652:Mesoporphyrins / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology; D011108:Polymers; D014407:Tumor Cells, Cultured
D003287:Contrast Media; D008652:Mesoporphyrins; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011108:Polymers; C088297:meso-chlorin e(6) monoethylene diamine; C090600:gadobutrol