MacDiarmid, J. A., Mugridge, N. B., Weiss, J. C., Phillips, L., Burn, A. L., Paulin, R. P., Haasdyk, J. E., Dickson, K. A., Brahmbhatt, V. N., Pattison, S. T., James, A. C., Al Bakri, G., Straw, R. C., Stillman, B., Graham, R. M., Brahmbhatt, H. (May 2007) Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics. Cancer Cell, 11 (5). pp. 431-445. ISSN 1535-6108
Abstract
Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | EPIDERMAL-GROWTH-FACTOR ESCHERICHIA-COLI FACTOR RECEPTOR DRUG-DELIVERY EFFLUX PUMPS TUMOR-CELLS IN-VIVO PERMEABILITY DIVISION EFFICACY |
| Subjects: | Investigative techniques and equipment > microspheres therapies organism description > bacteria organism description > bacteria > escherichia coli |
| CSHL Authors: | |
| Communities: | CSHL labs > Stillman lab |
| Highlight: | Stillman, Bruce W. |
| Depositing User: | CSHL Librarian |
| Date: | May 2007 |
| Date Deposited: | 11 Nov 2011 16:06 |
| Last Modified: | 20 Jun 2017 16:44 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/23088 |
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