Abstract
Multifunctional drug delivery systems(DDSs)have shown great prospects in overcoming the heteroge-neous barrier of delivery drugs to the complex tumor microenvironment(TME).In this study,multifunc-tional AS/Ge-pNAB microgels with dual-active targeting,triple environment responsiveness,and fluores-cence imaging capability were prepared through a straightforward procedure.This was aimed to improve the antitumor therapeutic application of gambogic acid(GA)based on the biological characteristics of TME.The microgels have a uniform double-layer structure with aptamer in the outer layer which helps in recognizing receptors on the tumor cells.The GA loaded nano-herb exhibited environment-responsive drug release profiles under acidic pH,reductant and high temperature.The nano-herb significantly im-proved the accumulation of GA in tumor sites through the synergistic combination of the enhanced per-meability and retention effect and dual-ligand mediated internalization.Then,it accelerated intracellular drug release and killed tumor cells.Therefore,the nano-herb had specific therapeutic effects on the tu-mor in vitro and in vivo as they remarkably inhibited tumor growth while depicting optimal biosafety and lower levels of off-target toxicity.Overall,these findings demonstrate the great potential of the mul-tifunctional AS/Ge-pNAB microgels for precisely targeted GA delivery and open a new avenue for the facile preparation of multifunctional DDSs.
基金项目
国家自然科学基金(21907076)
国家自然科学基金(31901908)
天津市自然科学基金(22JCQNJC01570)
Scientific Project of Tianjin Municipal Education Commission(2022KJ026)