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 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.
MacDiarmid
Jennifer A
JA
EnGeneIC Pty Ltd, North Ryde, Sydney, Australia.
Madrid-Weiss
Jocelyn
J
Amaro-Mugridge
Nancy B
NB
Phillips
Leo
L
Brahmbhatt
Himanshu
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D001419:Bacteria / Q000166:cytology*; D002453:Cell Cycle / Q000187:drug effects; D004285:Dogs; D016503:Drug Delivery Systems; D004349:Drug Packaging; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D051379:Mice; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy*