Tumor-targeting nanoimmunoliposome complex for short interfering RNA delivery.
The potential of short interfering RNA (siRNA) to be developed for therapeutic use against cancer depends on the availability of an efficient tumor-specific delivery vehicle. We have previously shown that a nanoscale nonviral liposome-based complex that includes an anti-transferrin receptor single-chain antibody fragment as the targeting moiety can, when systemically administered, specifically and efficiently target primary and metastatic tumors and deliver molecules useful in gene medicine, including plasmid DNA and antisense oligonucleotides. Here we explore the ability of this complex to deliver a fluorescein-labeled siRNA to tumor cells in vivo and examine the intracellular localization in vitro by confocal microscopy. We show that the immunoliposome--siRNA complex maintains its nanoscale size and, using three separate tumor models, can efficiently and specifically deliver siRNA to both primary and metastatic disease after systemic delivery, thus increasing the possibility for translating the potent effects of siRNA observed in vitro into clinically useful therapeutics.
Pirollo
Kathleen F
KF
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Zon
Gerald
G
Rait
Antonina
A
Zhou
Qi
Q
Yu
Wei
W
Hogrefe
Richard
R
Chang
Esther H
EH
D000818:Animals; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D005834:Genital Neoplasms, Male / Q000556:secondary; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D049329:Nanostructures; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D012669:Seminal Vesicles; D012680:Sensitivity and Specificity
D008081:Liposomes; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin