Abstract |
Two complementary coiled-coil peptides CCE/CCK are used to develop a " drug free" therapeutic system, which can specifically kill cancer cells without a drug. CCE is attached to the Fab' fragment of anti-CD20 1F5 antibody (Fab'-CCE), and CCK is conjugated in multiple grafts to poly[N-(2-hydroxypropyl) methacrylamide] (P-(CCK)x ). Two conjugates are consecutively administered: First, Fab'-CCE coats peptide CCE at CD20 antigen of lymphoma cell surface; second, CCE/CCK biorecognition between Fab'-CCE and P-(CCK)x leads to coiled-coil formation, CD20 crosslinking, membrane reorganization, and ultimately cell apoptosis. To prove that two conjugates can assemble at cell surface, multiple fluorescence imaging studies are performed, including 2-channel FMT, 3D confocal microscopy, and 4-color FACS. Confocal microscopy shows colocalization of two fluorescently labeled conjugates on non-Hodgkin's lymphoma (NHL) Raji cell surface, indicating "two-step" targeting specificity. The fluorescent images also reveal that these two conjugates can disrupt normal membrane lipid distribution and form lipid raft clusters, leading to cancer cell apoptosis. This "two-step" biorecognition capacity is further demonstrated in a NHL xenograft model, using fluorescent images at whole-body, tissue and cell levels. It is also found that delaying injection of P-(CCK)x can significantly enhance targeting efficacy. This high-specificity therapeutics provide a safe option to treat NHL and other B cell malignancies.
|
Authors | Rui Zhang, Jiyuan Yang, Te-Wei Chu, Jonathan M Hartley, Jindřich Kopeček |
Journal | Advanced healthcare materials
(Adv Healthc Mater)
Vol. 4
Issue 7
Pg. 1054-65
(May 2015)
ISSN: 2192-2659 [Electronic] Germany |
PMID | 25612325
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Copyright | © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Chemical References |
- Acrylamides
- Antigens, CD20
- Immunoglobulin Fab Fragments
- Lipids
- Membrane Lipids
- Peptides
- N-(2-hydroxypropyl)methacrylamide
|
Topics |
- Acrylamides
(immunology)
- Animals
- Antigens, CD20
(immunology)
- Apoptosis
(drug effects, immunology)
- Cell Line, Tumor
- Female
- Fluorescence
- Humans
- Immunoglobulin Fab Fragments
(immunology)
- Lipids
(immunology)
- Lymphoma
(drug therapy, immunology)
- Membrane Lipids
(immunology)
- Mice, Nude
- Mice, SCID
- Multimodal Imaging
(methods)
- Peptides
(immunology, therapeutic use)
|