In Vivo Delivery of Bionanocapsules Displaying Phaseolus vulgaris Agglutinin-L 4 Isolectin to Malignant Tumors Overexpressing N -Acetylglucosaminyltransferase V

Abstract

Metastasis is a key aspect of tumor malignancy, and several malignant tumors show expression of various mature N-type glycans. In particular, β1-6 branching N-acetylglucosamine (GlcNAc) is abundantly expressed as a part of high-mannose glycans in various highly metastatic cancers. Phaseolus vulgaris agglutinin-L₄ isolectin (L₄-PHA), which adheres to β1-6 GlcNAc specifically, has been used for in situ cancer diagnosis. Bionanocapsules (BNCs), hollow particles with a diameter of approximately 80 nm and composed of hepatitis B surface antigen (HBsAg) and a lipid bilayer, have been developed as human liver-specific nanocapsules for in vivo drug delivery system. In this study, we have generated L₄-PHA-displaying BNCs (PHA–BNCs) and examined whether L₄-PHA could retarget the BNCs to malignant tumors as a “biosensor” distinguishing tumor metastaticity. Fluorescence-labeled PHA–BNCs injected systemically into a mouse xenograft model were found to accumulate in β1-6 GlcNAc-expressing malignant tumors. The PHA–BNCs were able to deliver DNA to the malignant cancer cells. These results open up the possibility of using L₄-PHA lectin as a targeting molecule in a drug delivery system, and of using PHA–BNCs as a novel nanodevice for malignant tumor-specific bioimaging and drug delivery.