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Proceedings Paper

Photodynamic therapy with simultaneous suppression of multiple treatment escape pathways (Conference Presentation)
Author(s): Bryan Q. Spring; R. Bryan Sears; Lei Z. Zheng; Zhiming Mai; Reika Watanabe; Margaret E. Sherwood; David A. Schoenfeld; Brian W. Pogue; Stephen P. Pereira; Elizabeth Villa; Tayyaba Hasan

Paper Abstract

We introduce photoactivatable multi-inhibitor nanoliposomes (PMILs) for photodynamic tumor cell and microvessel damage in synchrony with photo-initiation of tumor-confined, multikinase inhibitor release. The PMIL is a biodegradable delivery system comprised of a nanoliposome carrying a photoactivable chromophore (benzoporphyrin derivative monoacid A, BPD) in its bilayer. A multikinase inhibitor-loaded PEG-PLGA nanoparticle is encapsulated within the liposome, which acts a barrier to nanoparticle erosion and drug release. Following intravenous PMIL administration, near infrared irradiation of tumors triggers photodynamic therapy and initiates tumor-confined drug release from the nanoparticle. This talk presents promising preclinical data in mouse models of pancreatic cancer utilizing this concept to suppress the VEGF and MET signaling pathways—both critical to cancer progression, metastasis and treatment escape. A single PMIL treatment using low doses of a multikanse inhibitor (cabozantinib, XL184) achieves sustained tumor reduction and suppresses metastatic escape, whereas combination therapy by co-administration of the individual agents has significantly reduced efficacy. The PMIL concept is amenable to a number of molecular inhibitors and offers new prospects for spatiotemporal synchronization of combination therapies whilst reducing systemic drug exposure and associated toxicities.

Paper Details

Date Published: 26 April 2016
PDF: 1 pages
Proc. SPIE 9694, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 969409 (26 April 2016); doi: 10.1117/12.2213828
Show Author Affiliations
Bryan Q. Spring, Massachusetts General Hospital (United States)
R. Bryan Sears, Massachusetts General Hospital (United States)
Lei Z. Zheng, Massachusetts General Hospital (United States)
Zhiming Mai, Massachusetts General Hospital (United States)
Reika Watanabe, Univ. of California, San Diego (United States)
Margaret E. Sherwood, Massachusetts General Hospital (United States)
David A. Schoenfeld, Massachusetts General Hospital (United States)
Brian W. Pogue, Thayer School of Engineering at Dartmouth (United States)
Stephen P. Pereira, Univ. College London (United Kingdom)
Elizabeth Villa, Univ. of California, San Diego (United States)
Tayyaba Hasan, Massachusetts General Hospital (United States)

Published in SPIE Proceedings Vol. 9694:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV
David H. Kessel; Tayyaba Hasan, Editor(s)

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