DNAzyme-adsorbed polydopamine@MnO2 core–shell nanocomposites for enhanced photothermal therapy via the self-activated suppression of heat shock protein 70

Photothermal therapy (PTT) is a promising tumor treatment modality, but its efficacy is strictly hindered by abnormally upregulated heat shock proteins (HSPs) in tumor cells under heat stress. Herein, we developed a flower-like MnO2-coated polydopamine (PDA@MnO2) core-shell nanoplatform with the surface adsorption of HSP70-silencing DNAzyme (DZ) for enhanced PPT. The PDA core acted as a robust photothermal agent, and also as a reductant to allow the surface growth of MnO2via an in situ reduction of KMnO4. The MnO2 shell enabled a rapid and efficient adsorption of DZ, and more importantly, acted as a metal reservoir to release Mn2+ in response to intracellular stimuli for the in situ activation of DZ, which addressed the key limitation of DZ for biological applications, i.e., metal-dependent activity. As a result, HSP70 was remarkably suppressed for improved PTT efficacy upon laser irradiation, which was explicitly demonstrated both in vitro and in vivo. Upon intravenous injection, the nanosystem could effectively accumulate in the tumor, and impose potent PTT for complete tumor elimination via inducing tumor cell apoptosis, but without any noticeable toxicity. This work provides a promising nanosystem for enhanced PTT via silencing resistance-related genes, and offers ideas for the design of self-activated gene therapy platforms using DZ.