To improve the therapeutic efficacy of
gemcitabine (GEM) as an anticancer
drug for
bile duct cancer, GEM-loaded
liposomes (GDPPL) prepared from a
photosensitizer-conjugated
lipid were investigated regarding the drug release kinetics,
photodynamic therapy (
PDT) efficacy, and immunomodulatory effects. The release rate of GEM from the
liposomes was improved approximately 2-fold compared to non-
laser irradiation groups due to
lipid disruption by
reactive oxygen species produced from the activated
photosensitizer upon
laser irradiation. Through in vitro testing using a human liver bile duct
carcinoma cell line (HuCCT-1), the cytotoxicity of GDPPL with
laser irradiation was enhanced due to rapid GEM release and
PDT effects. Furthermore, the results of in vivo tests using a HuCCT-1
tumor-bearing xenograft mice model showed that GDPPL exhibited approximately 3-fold antitumoral effects compared to control group. Additionally, immunohistochemical analysis demonstrated the recruitment of immunostimulatory cells in
tumor tissues. IHC tests in BALB/c mice indicated that GDPPL under
laser irradiation dramatically enhanced the quantities of various immune cells for effective antitumoral
immunotherapy against
biliary tract cancer. From these results, it was concluded that GDPPL with rapid drug release behavior,
PDT efficacy, and immunomodulatory effects upon
laser irradiation has potential as an antitumor therapeutic agent for
biliary tract cancer.