Polymer coated nanodiamonds as gemcitabine prodrug with enzymatic sensitivity for pancreatic cancer treatment
Wanying Ye, Haijie Han, Huan Li, Qiao Jin, Yuzhou Wu, Sabyasachi Chakrabortty, Tanja Weil, Jian Ji
Abstract
The fabrication of Gemcitabine (GEM) prodrug was reported to be an effective method to enhance its pancreatic cancer treatment efficiency. Here, a kind of nanocarbon-based materials, nanodiamond (ND), was selected as the nanocarrier of GEM, owing to its outstanding surface properties and non-cytotoxicity. The polyelectrolytes, polyethyleneimine and polyacrylic acid, were used to self-assemble outside ND surface through electrostatic forces, followed by attachment of polyethylene glycol to address better biocompatibility. GEM was conjugated with an enzyme-sensitive peptide gly-phe-leu-gly to build up the controlled release platform. From characterization results of dynamic laser scattering, zeta potential and transmission electron microscope, the significant improvement of ND stability in physiological condition was proved. Non-cytotoxicity of this functionalized ND carriers and cytotoxicity of the prodrug against BxPC-3 pancreatic cancer cells were indicated by methylthiazolyl tetrazolium (MTT) assay. In vivo experiments also revealed its superior anticancer effect compared with free GEM treatment. Therefore, the combination of polymer coated NDs with high surface capability and enzyme-responsive intracellular GEM release make it possible to realize higher treatment efficiency on pancreatic tumor therapy.