Creating Structural Defects of Drug-Free Copper-Containing Layered Double Hydroxide Nanoparticles to Synergize Photothermal/Photodynamic/Chemodynamic Cancer Therapy

Combination therapy has been extensively studied to achieve a more efficient inhibition of tumor progression. Herein, a nanoplatform based on layered double hydroxide (LDH) nanoparticles (NPs) is specifically constructed for the effective combination breast cancer therapy without the traditional anticancer drug. Cu-containing LDH NPs loaded with indocyanine green (ICG) are devised with more Cu coordination defects (d-Cu-LDH/ICG) to induce photothermal/photodynamic/chemodynamic therapy (PTT/PDT/CDT) using only one laser source. The structurally created defects on the LDH surface and dual-function ICG molecules in the LDH interlayer significantly enhance photothermal transduction and singlet-oxygen (O-1(2)) generation at 808 nm laser irradiation. Moreover, d-Cu-LDH/ICG NPs generate hydroxyl radicals (center dot OH) in the presence of H2O2 as Fenton catalysts, which are further enhanced by Cu(II) reduction with glutathione and temperature elevation. Consequently, d-Cu-LDH/ICG NPs significantly suppress 4T1 cell proliferation and show effective inhibition of the tumor growth in vivo through only one combined PTT/PDT/CDT under very mild laser irradiation, i.e., at 0.23 W cm(-2) for 5 min with very low doses of Cu and ICG (2.5 and 0.5 mg kg(-1)). Altogether, the defect-created d-Cu-LDH/ICG nanoplatform offers a new and safe treatment option for combination cancer therapy without using any anticancer drugs.

Automated summary

A nanoplatform based on LDH nanoparticles has been developed for combined breast cancer therapy without traditional anticancer drugs, utilizing photothermal/photodynamic/chemodynamic therapy. By enhancing photothermal transduction and singlet-oxygen generation, the nanoplatform effectively inhibits tumor growth with low doses of Cu and ICG under mild laser irradiation.