In vivo delivery of bionanocapsules displaying Phaseolus vulgaris agglutinin-L4 isolectin to malignant tumors overexpressing N-acetylglucosaminyltransferase V

Hum Gene Ther. 2008 Sep;19(9):887-95. doi: 10.1089/hum.2008.037.

Abstract

Metastasis is a key aspect of tumor malignancy, and several malignant tumors show expression of various mature N-type glycans. In particular, beta1-6 branching N-acetylglucosamine (GlcNAc) is abundantly expressed as a part of high-mannose glycans in various highly metastatic cancers. Phaseolus vulgaris agglutinin-L(4) isolectin (L(4)-PHA), which adheres to beta1-6 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 L(4)-PHA-displaying BNCs (PHA-BNCs) and examined whether L(4)-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 beta1-6 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 L(4)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • DNA, Recombinant / administration & dosage
  • DNA, Recombinant / genetics
  • Drug Delivery Systems
  • Genetic Therapy / methods
  • Humans
  • Liver Neoplasms, Experimental / diagnosis
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / secondary
  • Male
  • Mice
  • Mice, Nude
  • N-Acetylglucosaminyltransferases / metabolism
  • Nanocapsules
  • Neoplasm Transplantation
  • Neoplasms / diagnosis*
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Phaseolus
  • Phytohemagglutinins / administration & dosage*
  • Phytotherapy
  • Transplantation, Heterologous

Substances

  • DNA, Recombinant
  • Nanocapsules
  • Phytohemagglutinins
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase