title: Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics.
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.
authors.affiliation: EnGeneIC Pty Ltd., 105 Delhi Road, North Ryde, Sydney, NSW 2113, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: MacDiarmid
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Mugridge
authors.forename: Jocelyn C
authors.initials: JC
authors.lastname: Weiss
authors.forename: Leo
authors.initials: L
authors.lastname: Phillips
authors.forename: Adam L
authors.initials: AL
authors.lastname: Burn
authors.forename: Richard P
authors.initials: RP
authors.lastname: Paulin
authors.forename: Joel E
authors.initials: JE
authors.lastname: Haasdyk
authors.forename: Kristie-Ann
authors.initials: KA
authors.lastname: Dickson
authors.forename: Vatsala N
authors.initials: VN
authors.lastname: Brahmbhatt
authors.forename: Scott T
authors.initials: ST
authors.lastname: Pattison
authors.forename: Alexander C
authors.initials: AC
authors.lastname: James
authors.forename: Ghalib
authors.initials: G
authors.lastname: Al Bakri
authors.forename: Rodney C
authors.initials: RC
authors.lastname: Straw
authors.forename: Bruce
authors.initials: B
authors.lastname: Stillman
authors.forename: Robert M
authors.initials: RM
authors.lastname: Graham
authors.forename: Himanshu
authors.initials: H
authors.lastname: Brahmbhatt
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001419:Bacteria; D045744:Cell Line, Tumor; D004285:Dogs; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D013552:Swine
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents