Systemic Delivery of siRNA by Chimeric Capsid Protein: Tumor Targeting and RNAi Activity <i>in Vivo</i>

다국어 초록 (Multilingual Abstract)

<P>Recently, we reported that a chimeric capsid protein assembled into a macromolecular container-like structure with capsid shell and the resulting siRNA/capsid nanocarrier complexes efficiently suppressed RFP gene expression in the cell culture system. To extend RNAi to the <I>in vivo</I> applications, we here demonstrated that the siRNA/capsid nanocarrier complexes could have tumor-specific targeting ability <I>in vivo</I> as well as the increased stability of siRNA during body circulation. When systemically administered, our siRNA/capsid nanocarrier complexes delivered siRNA to tumor tissues and efficiently suppressed RFP gene expression in tumor-bearing mice. The enhanced longevity of siRNA <I>in vivo</I> could be explained by shielding effect derived from the capsid shell, where the encapsulated siRNAs are protected from nucleases in plasma. The multivalent RGD peptides on shell surface, as a result of self-assembling of capsid protein subunits, showed efficient delivery of siRNA to the tumor tissues <I>in vivo</I>, due to the RGD-mediated binding to integrin receptors overexpressed on tumor cells. Moreover, the prolonged <I>in vivo</I> circulation time of our siRNA/capsid nanocarrier complexes increased the potential to serve as siRNA carriers for optimal <I>in vivo</I> RNAi. These results provide an alternative approach to systemically deliver siRNA to the tumor sites as well as to enhance the stability of siRNA <I>in vivo</I>. Therefore, our results revealed the promising potential of our capsid nanocarrier system as a therapeutic siRNA carrier for cancer treatment.</P><P><B>Graphic Abstract</B>
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