Tumor-targeting core-shell structured nanoparticles for drug procedural controlled release and cancer sonodynamic combined therapy.

Abstract Combination therapy with multiple drugs or/and multiple assistant treatments has become a hot spot in cancer therapy. In this study, a new type of core-shell structured dual-drug delivery system based on poly (lactic- co -glycolic acid) (PLGA, inner cores) and hyaluronic acid (HA, outer shells) was constructed. Firstly, HA was conjugated to PLGA for preparation of HA-PLGA block copolymer. Secondly, 5-amino levulinic acid (ALA) was connected to PLGA through a pH-sensitive hydrazone bond for synthesization of PLGA-HBA-ALA. Finally, the core-shell structured nanoparticles (HA-PLGA@ART/ALA NPs) were constructed by self-assembled method for artemisinin (ART) loading in PLGA cores. In this co-delivery system, ALA and ART can be released in a manner of procedural controlled release. ALA was released from the NPs at first though the pH sensitive hydrazone bond cleavage in order to generate protoporphyrin IX (PpIX) for heme formation. And the increase of heme can effectively improve the curative effect of the subsequent released ART. Furthermore, this system has also shown obvious sonodynaimc activity which can be used for cancer sonodynamic combination therapy. The in vitro and in vivo anticancer results demonstrate that HA-PLGA@ART/ALA delivery system could provide a prospective comprehensive treatment strategy for cancer therapy. Graphical abstract A tumor-targeting drug delivery system based on the PLGA nanoparticles for ART and ALA dual-drug delivery and sonodynamic combination cancer therapy. Unlabelled Image Highlights • The dual drug delivery system has drug procedural controlled release function. • 5-amino levulinic acid can generate protoporphyrin IX for heme formation. • The increase of heme can effectively improve the curative effect of artemisinin. • The delivery system can be used for cancer sonodynamic combination therapy. [ABSTRACT FROM AUTHOR]