Deoxyribozyme-nanosponges for improved photothermal therapy by overcoming thermoresistance

Abstract

Thermoresistance shields cancer cells from damage by hyperthermia, decreasing the efficacy of photothermal therapy. Therefore, the design of photothermal therapeutic systems that avoid inducing thermoresistance is highly desirable for precision medicine. Herein, by simply assembling a cationic polymer and a long single strand of DNA encoded with multivalent deoxyribozyme (or DNAzyme) sequences, we have developed a sponge-like nanoplatform for highly efficient photothermal therapy that uses DNAzymes to overcome thermal resistance. The multivalent customized DNAzymes can catalytically cleave HSP70 mRNAs and downregulate the expression of their proteins, which protect MCF-7 cells from damage by hyperthermia. In vitro and in vivo studies have demonstrated the capability of this therapeutic platform to sensitize MCF-7 cells to heat by inhibiting the overexpression of HSP70. In addition, the nanoplatform can act as an efficient multimode imaging agent to trace its accumulation in tumor tissue.