4 years ago

Oral siRNA Delivery to Treat Colorectal Liver Metastases

Oral siRNA Delivery to Treat Colorectal Liver Metastases
Sung Hun Kang, Vishnu Revuri, Sungpil Cho, Yong-kyu Lee, Kwang Jae Cho, Woo Kyun Bae, Sang-Joon Lee, In-Kyu Park
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.

Publisher URL: http://dx.doi.org/10.1021/acsnano.7b05547

DOI: 10.1021/acsnano.7b05547

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