Hierarchical Two-Dimensional Layered Double Hydroxide Coated Polydopamine Nanocarriers for Combined Chemodynamic and Photothermal Tumor Therapy

Abstract

The combination of chemodynamic therapy (CDT) and photothermal therapy (PTT) has proven to be successful in combating the challenges associated with cancer therapy. A combination of these therapies can maximize the benefits of each therapeutic modality through endogenous reduction-oxidation (redox) reaction and external laser power induction. In the current work, we have designed a copper-aluminum layered double hydroxide (CuAl-LDH) loaded doxorubicin (DOX) by a co-precipitation method; the surface was coated with polydopamine (PDA). The synthesized CuAl-LDH@DOX@PDA nanocarrier (NC) served as a Fenton-like catalyst with photothermal properties. It is well known that metal ion incorporated NCs can induce intracellular depletion of reduced glutathione (GSH) levels along with the reduction of Cu2+ to Cu+. The Cu+ ions in turn react with DOX leading to the generation of intracellular hydrogen peroxide (H2O2) molecules to produce the highly toxic hydroxyl radicals (•OH) through a Fenton-like reaction. The enhanced absorption of CuAl@DOX@PDA at 810 nm, greatly improved the photothermal efficiency in comparison with bare CuAl-LDH and CuAl-LDH@DOX. In vitro studies revealed the tremendous CDT/PTT efficacy of CuAl@DOX@PDA in suppressing A549 cancer cells. Furthermore, reactive oxygen species (ROS) assays and intracellular levels of various ROS cascade biomolecules support our findings in the efficient destruction of cancer cells through synergistic CDT/PTT therapy.