Bacterially-Derived Nanocells for Tumor-Targeted Delivery of Chemotherapeutics and Cell Cycle Inhibitors

Chemotherapeutic drug therapy in cancer is seriously hampered by severe toxicity primarily due to indiscriminate drug distribution and consequent collateral damage to normal cells. Molecularly targeted drugs such as cell cycle inhibitors are being developed to achieve a higher degree of tumor cell s...

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Published inCell cycle (Georgetown, Tex.) Vol. 6; no. 17; pp. 2099 - 2105
Main Authors MacDiarmid, Jennifer A., Madrid-Weiss, Jocelyn, Amaro-Mugridge, Nancy B., Phillips, Leo, Brahmbhatt, Himanshu
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 01.09.2007
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Abstract Chemotherapeutic drug therapy in cancer is seriously hampered by severe toxicity primarily due to indiscriminate drug distribution and consequent collateral damage to normal cells. Molecularly targeted drugs such as cell cycle inhibitors are being developed to achieve a higher degree of tumor cell specificity and reduce toxic side effects. Unfortunately, relative to the cytotoxics, many of the molecularly targeted drugs are less potent and the target protein is expressed only at certain stages of the cell cycle thus necessitating regimens like continuous infusion therapy to arrest a significant number of tumor cells in a heterogeneous tumor mass. Here we discuss targeted drug delivery nanovectors and a recently reported bacterially-derived 400nm sized minicell that can be packaged with therapeutically significant concentrations of chemotherapeutic drugs, targeted to tumor cell surface receptors and effect intracellular drug delivery with highly significant anti-tumor effects in-vivo. We also report that molecularly targeted drugs can also be packaged in minicells and targeted to tumor cells with highly significant tumor growth-inhibition and regression in mouse xenografts despite administration of minute amounts of drug. This targeted intracellular drug delivery may overcome many of the hurdles associated with the delivery of cytotoxic and molecularly targeted drugs.
AbstractList Chemotherapeutic drug therapy in cancer is seriously hampered by severe toxicity primarily due to indiscriminate drug distribution and consequent collateral damage to normal cells. Molecularly targeted drugs such as cell cycle inhibitors are being developed to achieve a higher degree of tumor cell specificity and reduce toxic side effects. Unfortunately, relative to the cytotoxics, many of the molecularly targeted drugs are less potent and the target protein is expressed only at certain stages of the cell cycle thus necessitating regimens like continuous infusion therapy to arrest a significant number of tumor cells in a heterogeneous tumor mass. Here we discuss targeted drug delivery nanovectors and a recently reported bacterially-derived 400nm sized minicell that can be packaged with therapeutically significant concentrations of chemotherapeutic drugs, targeted to tumor cell surface receptors and effect intracellular drug delivery with highly significant anti-tumor effects in-vivo. We also report that molecularly targeted drugs can also be packaged in minicells and targeted to tumor cells with highly significant tumor growth-inhibition and regression in mouse xenografts despite administration of minute amounts of drug. This targeted intracellular drug delivery may overcome many of the hurdles associated with the delivery of cytotoxic and molecularly targeted drugs.
Chemotherapeutic drug therapy in cancer is seriously hampered by severe toxicity primarily due to indiscriminate drug distribution and consequent collateral damage to normal cells. Molecularly targeted drugs such as cell cycle inhibitors are being developed to achieve a higher degree of tumor cell specificity and reduce toxic side effects. Unfortunately, relative to the cytotoxics, many of the molecularly targeted drugs are less potent and the target protein is expressed only at certain stages of the cell cycle thus necessitating regimens like continuous infusion therapy to arrest a significant number of tumor cells in a heterogeneous tumor mass. Here we discuss targeted drug delivery nanovectors and a recently reported bacterially-derived 400 nm sized minicell that can be packaged with therapeutically significant concentrations of chemotherapeutic drugs, targeted to tumor cell surface receptors and effect intracellular drug delivery with highly significant anti-tumor effects in vivo. We also report that molecularly targeted drugs can also be packaged in minicells and targeted to tumor cells with highly significant tumor growth-inhibition and regression in mouse xenografts despite administration of minute amounts of drug. This targeted intracellular drug delivery may overcome many of the hurdles associated with the delivery of cytotoxic and molecularly targeted drugs.
Author Madrid-Weiss, Jocelyn
Amaro-Mugridge, Nancy B.
Phillips, Leo
MacDiarmid, Jennifer A.
Brahmbhatt, Himanshu
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SubjectTerms Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Bacteria - cytology
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Cycle - drug effects
Cycle
Dogs
Drug Delivery Systems
Drug Packaging
Landes
Lymphoma, Non-Hodgkin - drug therapy
Mice
Nanotechnology
Neoplasms - drug therapy
Organogenesis
Proteins
Title Bacterially-Derived Nanocells for Tumor-Targeted Delivery of Chemotherapeutics and Cell Cycle Inhibitors
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http://www.landesbioscience.com/journals/cc/article/4648/
https://www.ncbi.nlm.nih.gov/pubmed/17786046
Volume 6
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