Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7866475 | Materials Science and Engineering: C | 2018 | 31 Pages |
Abstract
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 5.9â¯Î¼g/ml, 4.2â¯Î¼g/ml, 1.92â¯Î¼g/ml, and 0.45â¯Î¼g/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.
Related Topics
Physical Sciences and Engineering
Materials Science
Biomaterials
Authors
Wentao Yang, Qian Hu, Yanmei Xu, Hailang Liu, Lin Zhong,