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Tumor-targeting nanocomplex delivery of novel tumor suppressor RB94 chemosensitizes bladder carcinoma cells in vitro and in vivo.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2008 Apr 01; Vol. 14 (7), pp. 2190-8. - Publication Year :
- 2008
-
Abstract
- Purpose: RB94, a truncated form of RB110, has enhanced tumor suppressor potency and activity against all tumor types tested to date including bladder carcinoma. However, efficient, systemic delivery of the gene encoding RB94 specifically to tumors, is an obstacle to clinical application as an anticancer therapeutic. We have developed a systemically given, nanosized liposome DNA delivery system that specifically targets primary and metastatic disease. The ability of RB94, delivered via this nanocomplex, to sensitize bladder carcinoma to chemotherapy in vitro and in vivo was assessed.<br />Experimental Design: The nanocomplex is an RB94 plasmid encapsulated by a cationic liposome, the surface of which is decorated with a tumor-targeting moiety, either transferrin (Tf/Lip/RB94) or an antitransferrin receptor single-chain antibody fragment (TfRScFv/Lip/RB94). The ability of the complex to sensitize human bladder carcinoma HTB-9 cells to chemotherapeutics was assessed in vitro by XTT assay. In vivo tumor specificity and efficacy were tested in mice carrying HTB-9 tumors by PCR and tumor growth inhibition, respectively.<br />Results: Transfection with Tf/Lip/RB94 significantly sensitized HTB-9 cells to chemotherapeutic agents in vitro. Tumor specificity of the complex was shown in an orthotopic bladder tumor model by immunohistochemistry and PCR. Moreover, in mice bearing subcutaneous HTB-9 tumors, the combination of systemically given Tf/Lip/RB94 or TfRScFv/Lip/RB94 plus gemcitabine resulted in significant (P<0.0005) tumor growth inhibition/regression and induction of apoptosis.<br />Conclusions: Use of our tumor-targeting nanocomplex to specifically deliver the potent tumor suppressor RB94 efficiently to tumors has potential as a more effective treatment modality for genitourinary and other cancers.
- Subjects :
- Animals
Apoptosis drug effects
Cells, Cultured
Humans
Immunohistochemistry
Liposomes
Mice
Polymerase Chain Reaction
Retinoblastoma Protein administration & dosage
Transfection
Transferrin immunology
Transferrin metabolism
Xenograft Model Antitumor Assays
Immunoglobulin Fragments administration & dosage
Nanotechnology methods
Tumor Suppressor Proteins administration & dosage
Urinary Bladder Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 14
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 18381961
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-07-1951