Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics.
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.
MacDiarmid
Jennifer A
JA
EnGeneIC Pty Ltd., 105 Delhi Road, North Ryde, Sydney, NSW 2113, Australia.
Mugridge
Nancy B
NB
Weiss
Jocelyn C
JC
Phillips
Leo
L
Burn
Adam L
AL
Paulin
Richard P
RP
Haasdyk
Joel E
JE
Dickson
Kristie-Ann
KA
Brahmbhatt
Vatsala N
VN
Pattison
Scott T
ST
James
Alexander C
AC
Al Bakri
Ghalib
G
Straw
Rodney C
RC
Stillman
Bruce
B
Graham
Robert M
RM
Brahmbhatt
Himanshu
H
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
D000906:Antibodies; D000970:Antineoplastic Agents