Pillar[5]arene based prodrug as a GSH-responsive SO2 nanogenerator for effective gas cancer therapy

Sulfur dioxide (SO2), being one of the therapeutic gaseous molecules, has been widely utilized in cancer therapy because of its high therapeutic efficacy and biosafety. Nevertheless, the in situ-triggered and efficient transportation of SO2 to tumors are the main obstacles that restrict its clinical application. To overcome this impediment, we functionalized pillar[5]arene with 2,4-dinitrobenzene sulfonic acid (DNSB) and then self-assembled it with tetraphenyl-PEG (TPE-PEG) in aqueous media to form fluorescent nanoparticles (PSTPE NPs). Meanwhile, the target guest (NH2-PEG-FA) was encapsulated within the spacious cavity of pillar[5]arene via host-guest interaction. The resulting nanoparticles possess distinctive characteristics: (I) dual GSH recognition motifs for enhanced SO2 release kinetics; (II) incorporation of targeting ligands for selective cytotoxicity towards tumor cells while sparing normal tissues and cells; and (III) surface modification of pillar[5]arene with TPE-PEG conferring excellent dispersibility, biocompatibility, and fluorescence properties in aqueous environments. Collectively, this novel nanoparticle represents an innovative approach that utilizes macrocyclics as SO2 gas donors to induce cellular apoptosis and provides new insights into gas-based therapy. Pillar[5]arene based prodrug as a GSH-responsive SO2 nanogenerator was constructed successfully, which can further applied in cell-imaging and gas cancer therapy efficiently. [Display omitted]