| A novel approach to deliver anticancer drugs to key cell types in tumors using a PDGF receptor-binding cyclic peptide containing carrier. | |
| | |
MedLine Citation:
|
PMID: 20362019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Tumor stromal cells have been recently recognized to contribute to tumor growth. Therefore, we hypothesized that delivery of anticancer drugs to these cells in addition to the tumor cells might treat cancer more effectively. Stromal cells abundantly expressed Platelet-Derived Growth Factor Receptor-beta (PDGFR-beta) in different human tumors as shown with immunohistochemistry. To achieve targeting through PDGFR-beta, we developed a carrier by modifying albumin with a PDGFR-beta recognizing cyclic peptide (pPB-HSA). pPB-HSA specifically bound to PDGFR-beta-expressing 3T3 fibroblasts, C26 and A2780 cancer cells in vitro. Subsequently, doxorubicin was conjugated to pPB-HSA through an acid-sensitive hydrazone linkage. In vitro, Dox-HSA-pPB was taken up by fibroblasts and tumor cells and a short exposure of the conjugate induced cell death in these cells. In vivo, the conjugate rapidly accumulated into PDGFR-beta expressing cells in C26 tumors. Treatment with Dox-HSA-pPB significantly reduced the C26 tumor growth in mice while free doxorubicin treated mice had lower response to the therapy. Furthermore, in contrast to free doxorubicin the conjugate did not induce loss in body weight. In conclusion, the present study reveals a novel approach to target key cell types in tumors through PDGFR-beta, which can be applied to enhance the therapeutic efficacy of anticancer drugs. |
| | |
Authors:
|
Jai Prakash; Edwin de Jong; Eduard Post; Annette S H Gouw; Leonie Beljaars; Klaas Poelstra |
Related Documents
:
|
9702939 - Expression of e-cadherin and alpha-,beta- and gamma-catenins in human bladder carcinoma... 18077429 - Mast cells are an essential hematopoietic component for polyp development. 12131349 - Expression and prognostic value of cd44 isoforms in nephroblastoma (wilms tumor). 11676549 - Beta-catenin antisense treatment decreases beta-catenin expression and tumor growth rat... 2530299 - In vivo t cell tumor therapy with monoclonal antibody directed to the v beta chain of t... 17848589 - A proteomics analysis of cell signaling alterations in colorectal cancer. 19805119 - Impaired tumor growth, metastasis, angiogenesis and wound healing in annexin a1-null mice. 1863929 - Malignant choroid plexus papilloma of the iv ventricle. 11032019 - Human prolactin (hprl) antagonists inhibit hprl-activated signaling pathways involved i... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-31 |
Journal Detail:
|
Title: Journal of controlled release : official journal of the Controlled Release Society Volume: 145 ISSN: 1873-4995 ISO Abbreviation: J Control Release Publication Date: 2010 Jul |
Date Detail:
|
Created Date: 2010-07-12 Completed Date: 2011-01-13 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8607908 Medline TA: J Control Release Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 91-101 Citation Subset: IM |
Copyright Information:
|
Copyright (c) 2010 Elsevier B.V. All rights reserved. |
Affiliation:
|
Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands. J.Prakash@rug.nl |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antibiotics, Antineoplastic / pharmacology* Cell Line, Tumor Cell Survival / drug effects Colonic Neoplasms / drug therapy*, pathology Doxorubicin / pharmacology* Female Humans Mice NIH 3T3 Cells Ovarian Neoplasms / drug therapy*, pathology Peptides, Cyclic / genetics, metabolism, pharmacology Receptor, Platelet-Derived Growth Factor beta / metabolism*, physiology Serum Albumin / genetics, metabolism, pharmacology Stromal Cells / drug effects, metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Antibiotics, Antineoplastic; 0/Peptides, Cyclic; 0/Serum Albumin; 23214-92-8/Doxorubicin; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor beta |
| Comments/Corrections | |
Comment In:
|
J Control Release. 2010 Jul 14;145(2):75
[PMID:
20576503
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Functional analysis of the orf390 gene of the White Spot Syndrome Virus.
Next Document: Downregulation of EGFR by a novel multivalent nanobody-liposome platform.