Delivery of Cu(II) and Mn(II) by polydopamine-modified nanoparticles for combined photothermal and chemotherapy.

Abstract

Chemodynamic therapy (CDT) has been recognized as an emerging therapeutic strategy. It has attracted considerable attention in recent years as it can generate the most harmful reactive oxygen species (ROS)-hydroxyl radicals (•OH) through the Fenton reaction or a Fenton-like reaction under the catalysis of versatile metal cations, such as, Fe(II), Fe(III), Cu(I), Mn(II), and Mn(III). However, a large number of reducing species (e.g., GSH) in tumors inhibit the therapeutic effects of CDT. This study proposes a nanocarrier strategy that can release versatile metal cations in the initial stage to consume the reducing substances, which can be convenient for subsequent CDT treatment. A novel nano-delivery system based on H-MnO2@PDA/Cu-CD@Ad-TK-Ad@Ploy-CD (abbreviated as MNZ) was proposed to resolve the above problems. Herein, hollow mesoporous manganese dioxide nanoparticles (H-MnO2) were coated with PDA and modified with copper ions on the surface of PDA. The PDA was then functionalized with β-cyclodextrin (β-CD) substitutions that were further assembled with N-((1S,3R,5S)-adamantan-1-yl)-3-((2-((3-(((3s,5s,7s)-adamantan-1-yl)amino)-3-oxopropyl)thio)propan-2-yl)thio)propenamide (Ad-TK-Ad). Poly-CD was assembled with CD to improve the stability of the reactor. The MNZ nanotheranostic platform can release Cu(II) and Mn(II), which could react with intracellular GSH to consume the reducing substances in tumors. Subsequently, H2O2 can be converted into •OH, and the effect is improved with increasing temperatures. Cytotoxicity of MNZ (200 μg mL-1) was studied by cell counting kit-8 (CCK-8) assay using HeLa cells as the models. Results indicated that cell viability was clearly reduced to 22% by the nanoparticles alone, to 18% by the nanoparticles with H2O2, and to 9% by the nanoparticles with H2O2 and NIR, under weak acidic condition (pH 6.8). This work provides a beneficial exploration for the application of nano-delivery strategies for combined photothermal and chemodynamic therapy agents.