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Proceedings Paper

Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)
Author(s): Girgis Obaid; Yucheng Wang; Jerrin Kuriakose; Mans Broekgaarden; Ahmed Alkhateeb; Anne-Laure Bulin; James Hui; Andrew Tsourkas; Tayyaba Hasan
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Paper Abstract

Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for ‘click’ conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody’s Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody’s optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond conventional treatments.

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, 96940U (26 April 2016); doi: 10.1117/12.2214253
Show Author Affiliations
Girgis Obaid, Wellman Ctr. for Photomedicine (United States)
Yucheng Wang, Wellman Ctr. for Photomedicine (United States)
Jerrin Kuriakose, Wellman Ctr. for Photomedicine (United States)
Mans Broekgaarden, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School (United States)
Ahmed Alkhateeb, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School (United States)
Anne-Laure Bulin, Wellman Ctr. for Photomedicine (United States)
James Hui, Univ. of Pennsylvania (United States)
Andrew Tsourkas, Univ. of Pennsylvania (United States)
Tayyaba Hasan, Wellman Ctr. for Photomedicine (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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