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Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells.
- Source :
-
Molecular cancer therapeutics [Mol Cancer Ther] 2007 Oct; Vol. 6 (10), pp. 2737-46. - Publication Year :
- 2007
-
Abstract
- Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellularly delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line-dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs.
- Subjects :
- Antibiotics, Antineoplastic administration & dosage
Antineoplastic Agents administration & dosage
Antineoplastic Agents, Phytogenic administration & dosage
Cell Communication immunology
Cell Line, Tumor drug effects
Cell Survival drug effects
Doxorubicin administration & dosage
Flow Cytometry
Humans
Immunoglobulin Fragments immunology
Ligands
Liposomes
Male
Prostatic Neoplasms pathology
Radiation-Sensitizing Agents administration & dosage
Topotecan administration & dosage
Vinblastine administration & dosage
Vinblastine analogs & derivatives
Vinorelbine
Activated-Leukocyte Cell Adhesion Molecule immunology
Antibodies, Monoclonal administration & dosage
Drug Delivery Systems
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1535-7163
- Volume :
- 6
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular cancer therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 17938267
- Full Text :
- https://doi.org/10.1158/1535-7163.MCT-07-0140