Poly-thymine DNA templated MnO₂ biomineralization as a high-affinity anchoring enabling tumor targeting delivery

Manganese oxide nanomaterials (MONs) are emerging as a type of highly promising nanomaterials for diseases diagnosis, and surface modification is the basis for colloidal stability and targeting delivery of the nanomaterials. Here, we report the in-situ functionalization of MnO₂ with DNA through a biomineralization process. Using adsorption-oxidation method, DNA templated Mn²⁺ precursor to biomineralize into nano-cubic seed, followed by the growth of MnO₂ to form cube/nanosheet hybrid nanostructure. Among four types of DNA homopolymers, poly-thymine (poly-T) was found to stably attach on MnO₂ surface to resist various biological displacements (phosphate, serum, and complementary DNA). Capitalized on this finding, a di-block DNA was rationally designed, in which the poly-T block stably anchored on MnO₂ surface, while the AS1411 aptamer block was not only an active ligand for tumor targeting delivery, but also a carrier for photosensitizer (Ce6) loading. Upon targeting delivery into tumor cells, the MnO₂ acted as catalase-mimic nanozyme for oxygenation to sensitize photodynamic therapy, and the released Mn²⁺ triggered chemodynamic therapy via Fenton-like reaction, achieving synergistic anti-tumor effect with full biocompatibility. This work provides a simple yet robust strategy to functionalize metal oxides nanomaterials for biological applications via DNA-templated biomineralization.