1 research outputs found
CD44-Targeted Facile Enzymatic Activatable Chitosan Nanoparticles for Efficient Antitumor Therapy and Reversal of Multidrug Resistance
Nanoparticles
are attractive platforms for the delivery of various
anticancer therapeutics. Nevertheless, their applications are still
limited by the relatively low drug loading capacity and the occurrence
of multidrug resistance (MDR) against chemotherapeutics. In this study,
we report that the integration of d-α-tocopherol succinate
(VES) residue with both chitosan and paclitaxel (PTX) led to significant
improvement of drug loading capacity and drug loading efficiency through
the enhancement of drug/carrier interaction. After the incorporation
of hyaluronic acid containing PEG side chains (HA-PEG), higher serum
stability and more efficient cellular uptake were obtained. Due to
HA coating, VES residues and the enzymatic responsive drug release
property, such facile nanoparticles actively targeted cancer cells
that overexpress CD44 receptor and efficiently reversed the MDR of
treated cells, but caused no significant toxicity to mouse fibroblast
(NIH-3T3). More importantly, with HA-PEG coating, longer blood circulation
and more effective tumor accumulation were achieved for prodrug nanoparticles.
Finally, superior anticancer activity and excellent safety profile
was demonstrated by HA-PEG coated enzymatically activatable prodrug
nanoparticles compared to commercially available Taxol formulation