Targeting anticancer drug delivery to pancreatic cancer cells using a fucose-bound nanoparticle approach.
Owing to its aggressiveness and the lack of effective therapies, pancreatic ductal adenocarcinoma has a dismal prognosis. New strategies to improve treatment and survival are therefore urgently required. Numerous fucosylated antigens in sera serve as tumor markers for cancer detection and evaluation of treatment efficacy. Increased expression of fucosyltransferases has also been reported for pancreatic cancer. These enzymes accelerate malignant transformation through fucosylation of sialylated precursors, suggesting a crucial requirement for fucose by pancreatic cancer cells. With this in mind, we developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specifically to cancer cells. L-fucose-bound liposomes containing Cy5.5 or Cisplatin were effectively delivered into CA19-9 expressing pancreatic cancer cells. Excess L-fucose decreased the efficiency of Cy5.5 introduction by L-fucose-bound liposomes, suggesting L-fucose-receptor-mediated delivery. Intravenously injected L-fucose-bound liposomes carrying Cisplatin were successfully delivered to pancreatic cancer cells, mediating efficient tumor growth inhibition as well as prolonging survival in mouse xenograft models. This modality represents a new strategy for pancreatic cancer cell-targeting therapy.
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Makoto
M
Yoshida
Rishu
R
Takimoto
Kazuyuki
K
Murase
Yasushi
Y
Sato
Masahiro
M
Hirakawa
Fumito
F
Tamura
Tsutomu
T
Sato
Satoshi
S
Iyama
Takahiro
T
Osuga
Koji
K
Miyanishi
Kohichi
K
Takada
Tsuyoshi
T
Hayashi
Masayoshi
M
Kobune
Junji
J
Kato
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002232:Carbocyanines; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005260:Female; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D008081:Liposomes; D011956:Receptors, Cell Surface; C039707:galactose receptor; D005643:Fucose; D005647:Fucosyltransferases; D002945:Cisplatin