PH-controlled nucleolin targeted release of dual drug from chitosan-gold based aptamer functionalized nano drug delivery system for improved glioblastoma treatment

Abstract

This study developed the pH, and over-expressed nucleolin receptor responsive nano-drug delivery system (nDDS) composed by bio-synthesized gold nanoparticles (Au NPs), chitosan (CS) with aptamer (Apt) to deliver the 5-fluorouracil (5FU) and doxorubicin (Dox) for the improved glioblastoma treatment. The characterization results demonstrated that Apt-Dox-CS-Au-5FU NPs were monodispersed in nature with an average hydrodynamic particle size of 196.2 ± 2.89 nm and zeta potential of 16.26 ± 0.51 mV. The drug release, drug encapsulation efficiency (DEE), and loading efficiency (DLE) were measured by HPLC. The pH-responsive dual drug release was instigated the higher glioblastoma cell death instead of the single drug release through G0/G1 phase cell cycle arrest. In addition, the internalization of Apt-Dox-CS-Au-5FU NPs in cell organelles was affirmed by bio-TEM analysis. Overall, this work revealed the newly designed drug-loaded smart nDDS improved the glioblastoma treatments.