In vivo delivery of bionanocapsules displaying Phaseolus vulgaris agglutinin-L4 isolectin to malignant tumors overexpressing N-acetylglucosaminyltransferase V.
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.
Kasuya
Takeshi
T
Department of Structural Molecular Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
Jung
Joohee
J
Kadoya
Hiroyasu
H
Matsuzaki
Takashi
T
Tatematsu
Kenji
K
Okajima
Toshihide
T
Miyoshi
Eiji
E
Tanizawa
Katsuyuki
K
Kuroda
Shun'ichi
S
D000818:Animals; D045744:Cell Line, Tumor; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis / Q000188:drug therapy / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D053769:Nanocapsules; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000201:enzymology; D027805:Phaseolus; D010835:Phytohemagglutinins / Q000008:administration & dosage*; D008517:Phytotherapy; D014183:Transplantation, Heterologous
D004274:DNA, Recombinant; D053769:Nanocapsules; D010835:Phytohemagglutinins; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase