The development of nano-drug carriers primarily based on deoxyribonucleic acid (DNA) has demonstrated important therapeutic potential. Equally, supramolecular therapeutic techniques using host-guest interactions have emerged as a promising technique in nanomedicine. Constructing upon these approaches, we designed a size-controllable, multi-responsive supramolecular DNA nanogel (SDN) primarily based on host-guest recognition for dual-drug co-delivery in most cancers mixture remedy. The nanogel incorporates doxorubicin (DOX, a chemotherapeutic agent) and methylene blue (MB, a photosensitizer). The meeting of SDN is pushed by cucurbit[8]uril (CB[8]), which selectively binds two MB molecules—one from every of two Y-shaped DNA constructing blocks—forming a 1:2 host-guest advanced that crosslinks the constructions right into a nanogel community. In the meantime, the double-stranded DNA scaffold effectively encapsulates DOX through intercalation, enabling SDN@DOX to co-deliver each medicine in a exactly managed ratio. Notably, MB’s photodynamic exercise is initially suppressed upon CB[8] binding. Nonetheless, upon mobile uptake, SDN@DOX responds to overexpressed spermine or particular peptide sequences within the tumor microenvironment, triggering MB launch and restoring its photodynamic operate. Concurrently, DNase I-mediated DNA degradation liberates DOX, enabling synergistic chemo-photodynamic remedy (PDT). In vitro research confirmed that SDN@DOX enhances reactive oxygen species (ROS) era in most cancers cells and achieves superior therapeutic efficacy by mixed PDT and chemotherapy. This stimuli-responsive, dual-drug supply system affords a strong and controllable platform for precision most cancers remedy.
