Antibody fragment-conjugated gemcitabine and paclitaxel-based liposome for effective therapeutic efficacy in pancreatic cancer

In this study, we have developed an antibody fragment (AF)-conjugated gemcitabine (GEM) and paclitaxel (PTX)-loaded liposome (AF-GPL) to enhance the therapeutic efficacy in pancreatic cancer treatment. The maleimide-thiol chemistry was utilized to conjugate AF on the liposome surface. The dual-drug loaded liposome was nanosized and exhibited a controlled release of both the drugs. Importantly, two drugs have different release pattern over a period of time. The AF-conjugated liposome showed enhanced cellular uptake in pancreatic cancer cells compared to that of non-targeted liposome. Two-fold higher internalization of particles might increase the intracellular concentration of anticancer drugs that might further increase the therapeutic efficacy in pancreatic cancer cells. AF-GPL showed significantly higher cytotoxic effect in pancreatic cancer cell compared to that of non-targeted GPL. The IC50 value of GEM, PTX, GPL and AF-GPL were 5.9 μg/ml, 4.2 μg/ml, 1.92 μg/ml, and 0.45 μg/ml, respectively. Consistently, AF-GPL (4.12) showed significantly higher ratio of Bax/Bcl-2 compared to that of non-targeted GPL (2.8). Importantly, AF-GPL induced a significant apoptosis of cancer cells with predominant amount of cells in late apoptosis cells. Overall, AF-conjugated nanosystem could potentially improve the therapeutic efficacy in pancreatic cancers.