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For my fellow hardcore science geeks, nanocell targeted chemo delivery. Not ready for prime time in humans for quite a while, but technologies such as these give much hope for a future of low tox, tumor-specific cancer killing machines... and cures.
Cancer Cell Volume 11, Issue 5, 8 May 2007, Pages 431-445
Bacterially Derived 400 nm Particles for Encapsulation and Cancer Cell Targeting of Chemotherapeutics
Jennifer A. MacDiarmid1, Nancy B. Mugridge1, Jocelyn C. Weiss1, Leo Phillips1, Adam L. Burn1, Richard P. Paulin1, Joel E. Haasdyk1, Kristie-Ann Dickson1, Vatsala N. Brahmbhatt1, Scott T. Pattison1, Alexander C. James1, Ghalib Al Bakri1, Rodney C. Straw2, Bruce Stillman3, Robert M. Graham4, 5 and Himanshu Brahmbhatt1, ,
1EnGeneIC Pty Ltd, 105 Delhi Road, North Ryde, Sydney, NSW 2113, Australia
2Brisbane Veterinary Specialist Centre, Cnr. Old Northern Road and Keong Road, Albany Creek, Queensland 4035, Australia
3Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
4Victor Chang Cardiac Research Institute, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
5School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2054, Australia
Received 20 June 2006; revised 3 December 2006; accepted 15 March 2007. Published: May 7, 2007. Available online 7 May 2007.
Summary
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.
Author Keywords: CHEMBIO
Cancer Cell Volume 11, Issue 5, 8 May 2007, Pages 431-445
Bacterially Derived 400 nm Particles for Encapsulation and Cancer Cell Targeting of Chemotherapeutics
Jennifer A. MacDiarmid1, Nancy B. Mugridge1, Jocelyn C. Weiss1, Leo Phillips1, Adam L. Burn1, Richard P. Paulin1, Joel E. Haasdyk1, Kristie-Ann Dickson1, Vatsala N. Brahmbhatt1, Scott T. Pattison1, Alexander C. James1, Ghalib Al Bakri1, Rodney C. Straw2, Bruce Stillman3, Robert M. Graham4, 5 and Himanshu Brahmbhatt1, ,
1EnGeneIC Pty Ltd, 105 Delhi Road, North Ryde, Sydney, NSW 2113, Australia
2Brisbane Veterinary Specialist Centre, Cnr. Old Northern Road and Keong Road, Albany Creek, Queensland 4035, Australia
3Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
4Victor Chang Cardiac Research Institute, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
5School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2054, Australia
Received 20 June 2006; revised 3 December 2006; accepted 15 March 2007. Published: May 7, 2007. Available online 7 May 2007.
Summary
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.
Author Keywords: CHEMBIO
