1. Oral siRNA Delivery to Treat Colorectal Liver Metastases.
- Author
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Kang SH, Revuri V, Lee SJ, Cho S, Park IK, Cho KJ, Bae WK, and Lee YK
- Subjects
- Administration, Oral, Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Chitosan chemistry, Chitosan pharmacology, Colorectal Neoplasms pathology, Dogs, Drug Screening Assays, Antitumor, Female, Gold chemistry, Gold pharmacology, Humans, Liver Neoplasms pathology, Mice, Mice, Inbred BALB C, Nanoparticles chemistry, RNA, Small Interfering administration & dosage, RNA, Small Interfering chemistry, Taurocholic Acid chemistry, Taurocholic Acid pharmacology, Antineoplastic Agents pharmacology, Colorectal Neoplasms drug therapy, Drug Delivery Systems, Liver Neoplasms drug therapy, Liver Neoplasms secondary, RNA, Small Interfering pharmacology
- Abstract
Convenient multiple dosing makes oral administration an ideal route for delivery of therapeutic siRNA. However, hostile GI environments and nonspecific biological trafficking prevent achieving appropriate bioavailability of siRNA. Here, an orally administered AuNP-siRNA-glycol chitosan-taurocholic acid nanoparticle (AR-GT NPs) was developed to selectively deliver Akt2 siRNA and treat colorectal liver metastases (CLM). AR-GT NPs are dual padlocked nonviral vectors in which the initially formed AuNP-siRNA (AR) conjugates are further encompassed by bifunctional glycol chitosan-taurocholic acid (GT) conjugates. Covering the surface of AR with GT protected the Akt2 siRNA from GI degradation, facilitated active transport through enterocytes, and enhanced selective accumulation in CLM. Our studies in CLM animal models resulted in the reduction in Akt2 production, followed by initiation of apoptosis in cancer cells after oral administration of Akt2 siRNA-loaded AR-GT. This therapeutic siRNA delivery system may be a promising approach in treating liver-associated diseases.
- Published
- 2017
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