Bioluminescence resonance energy transfer using luciferase-immobilized quantum dots for self-illuminated photodynamic therapy.

Abstract

Photodynamic therapy (PDT) is an innovative method for cancer treatment that involves the administration of a photosensitizing agent followed by exposure to visible light. An appreciable amount of a particular light source is a key to activate photosensitizers in PDT. However, the external excitation light source is a problem for clinical application because of the limitation of tissue-penetrating properties. Additionally, the wavelength of laser emission should match the absorption wavelength of each photosensitizer for efficient generation of reactive oxygen species and cell killing. In this study, Renilla luciferase-immobilized quantum dots-655 (QD-RLuc8) was used for bioluminescence resonance energy transfer (BRET)-mediated PDT to resolve these problems. The bioluminescent QD-RLuc8 conjugate exhibits self-illumination at 655 nm after coelenterazine addition, which can activate the photosensitizer, Foscan(®)-loaded micelles for PDT. Our results show that BRET-mediated PDT by QD-RLuc8 plus coelenterazine (20 μg/mL) successfully generated reactive oxygen species (40.8%), killed ~ 50% A549 cells at 2 μg/mL equivalent Foscan(®)in vitro and significantly delayed tumor growth in vivo due to cell apoptosis under TUNEL analysis without obvious weight loss. Based on immunohistochemical observations, the proliferating cell nuclear antigen (PCNA)-negative area of tumor sections after BRET-mediated PDT was obviously increased compared to the PDT-untreated groups without an external light source. We conclude that this nanotechnology-based PDT possesses several clinical benefits, such as overcoming light penetration issues and treating deeper lesions that are intractable by PDT alone.

• Authors: Chia-Yen Hsu, Ching-Wen Chen, Hsiu-Ping Yu, Yan-Fu Lin, Ping-Shan Lai
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 4 Pg. 1204-12 (Jan 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23069718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Enzymes, Immobilized
• Mesoporphyrins
• Photosensitizing Agents
• Luciferases
• temoporfin

Topics

• Cell Line, Tumor
• Enzymes, Immobilized
• Fluorescence Resonance Energy Transfer (methods)
• Humans
• Luciferases (pharmacokinetics)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Mesoporphyrins (administration & dosage)
• Photochemotherapy (methods)
• Photosensitizing Agents (administration & dosage)
• Quantum Dots
• Treatment Outcome