Multifunctional nano-herb based on tumor microenvironment for enhanced tumor therapy of gambogic acid

Multifunctional drug delivery systems(DDSs)have shown great prospects in overcoming the heterogeneous barrier of delivery drugs to the complex tumor microenvironment(TME).In this study,multifunctional AS/Ge-pNAB microgels with dual-active targeting,triple environment responsiveness,and fluorescence 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 improved the accumulation of GA in tumor sites through the synergistic combination of the enhanced permeability 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 tumor 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 multifunctional AS/Ge-pNAB microgels for precisely targeted GA delivery and open a new avenue for the facile preparation of multifunctional DDSs.