PVA reinforced gossypolone and doxorubicin π–π stacking nanoparticles towards tumor targeting and ultralow dose synergistic chemotherapy†
To improve the tumor synergistic therapeutic effects of carrier-free dual-drug delivery systems and realize ultralow dose administration, we developed a tumor targeting and high-efficiency synergistic chemotherapy system (HA-Gn@DPGn NPs) based on polyvinyl alcohol (PVA) reinforced gossypolone (Gn) and doxorubicin (DOX) π–π stacking nanoparticles (DPGn NPs), in which PVA filled the gaps between Gn and DOX and bridged Gn and DOX tightly. Hyaluronic acid modifier hyaluronic acid-gossypolone (HA-Gn) was covered on the surface of DPGn NPs to form HA-Gn@DPGn NPs that procured active targeting properties. This system presented a spherical shape with a uniform hydrodynamic size of 87 ± 6.8 nm, a high drug loading of 80.31%, and high stability. FTIR and UV spectra demonstrated that HA-Gn was covered on the surface of the system and showed significant π–π stacking properties. A considerably low combination index of Gn and DOX (0.1862) was determined at an ultra-low dose of DOX under a Gn : DOX ratio of 50 : 1. HA-Gn@DPGn NPs also demonstrated excellent tumor synergistic therapeutic efficacy (TIR > 87%) at an ultralow dose of DOX and Gn. This system demonstrates high tumor comprehensive synergistic therapeutic efficacy at an ultralow drug dose with multiple favorable therapeutic characteristics, including negligible side effects, tumor targeting ability and thermal-responsive drug release, and thus has considerable potential for tumor synergistic therapy.