Photodynamic therapy( PDT) has extraordinary promise for the treatment of many cancers.H owever,i ts clinical progress is impaired by the intrinsic hypoxic tumor microenvironment that limits PDT efficacy and the safety concern associated with biological specificity of photosensitizers or vehicles.N ow it is demonstrated that rationally designed DNAn anosponges can load and delivery photosensitizer effectively,t arget tumor precisely,a nd relieve hypoxia-associated resistance remarkably to enhance the efficacy of PDT.S pecifically,t he approach exhibits af acile assembly process,p rovides programmable and versatile nanocarriers, and enables robust in vitro and in vivo anti-cancer efficacy with excellent biosafety.T hese findings represent ap ractical and safe approachb yd esigner DNAn anoassemblies to combat cancer effectively and suggest ap owerful strategy for broad biomedical application of PDT.

Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cell. However, elevated antioxidant defense systems in cancer cells give resistance to the therapy involved...

High mortality and rapid development of metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery, radiation therapy, and chemotherapy, show less effectiveness in curbing the metastatic spread of cancer cells and the formation of metastases. A therapeutic platform, targeting the early stage of metastasis cascade, could effectively prevent metastasis dissemination. Herein, Fe/Mn-based metal–organic frameworks (FMM) were constructed for the delivery of a specific DNAzyme with high catalytic cleavage activity on the metastasis-involved Twist mRNA, thus efficiently inhibiting the invasion of cancer cells through DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic therapy is achieved from the self-supplied DNAzyme cofactors and efficient glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist DNAzyme with efficient gene therapy. Consequently, the effective elimination of tumors and the blockage of metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile theranostic agents to combat metastatic tumors.

Unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides are immunostimulatory nucleic acids wildly utilized as adjuvants or for vaccines to treat diseases. However, there is a lack of simple and efficient vectors for CpG oligodeoxynucleotide delivery with long-lasting immune stimulation. Herein, self-assembled polymer wires consisting of CpG motifs by hybridization chain reaction were constructed with excellent biocompatibility and immunostimulatory activity. The designed polymer DNA wires acted as programmable multivalent immunoadjuvants and triggered immune response, stimulated pro-inflammatory cytokine secretion, and induced the apoptosis of cancer cells. More strikingly, polymer nanospheres assembled from the polymer DNA wires and cationic poly-l-lysine further improved cellular uptake and continuously stimulate the lysosomal Toll-like receptor 9 of immune cells, thereby remarkably enhancing the activation of immune cells. These results demonstrated that self-assembled polymer DNA nanoassemblies with multivalent CpG could trigger strong immune response and further induce cancer cell death.

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