PH and glutathione dual responsive nanoparticles based on Ganoderma lucidum polysaccharide for potential programmable release of three drugs

Abstract

Nanoparticles have been widely studied as carries of anti-cancer drugs, but designing and preparing smart drug delivery system for precisely controlled drug release remains a major challenge. Herein, a novel Ganoderma lucidum polysaccharides (GLP) based, rutin-carboxyphenyl boronic acid (CPBA)-GLP-dithiodipropionic acid (DPA)-dihydroartemisinin (DHA)/10-hydroxy camptothecin (HCPT) polymeric nanoparticles (RCGDDH NPs) with pH and redox dual-responsive were first presented. The three drugs loaded in RCGDDH NPs can be released programmatically: rutin is released in tumor tissue with acidic microenvironment, DHA and HCPT are released in the redox environment in tumor cells. Interestingly, GLP, as a carrier, has anti-cancer activity and can enhance anti-cancer activity. Size of the RCGDDH NPs prepared is about 98 nm. The in vitro release study shows when under the condition of pH 5.2 and 10 mM reductive glutathione, the amount of HCPT and DHA released from nanoparticles is 2.5 and 2.7 folds higher than the normal physiological condition. In addition, rutin in the nanoparticles can be released in a slightly acidic condition and has an obvious inhibitory action of matrix metalloproteinase MMP-9. Further, in vitro and in vivo experiments indicate that the prepared RCGDDH NPs can effectively kill tumor cells, inhibit tumor growth and cause low side effects. The above results suggest that the pH and redox dual-responsive RCGDDH NPs are a promising candidate for tumor therapy.