Acid-responsive DNA-Au nanomachine with active/passive dual-targeting capacity for combinational cancer therapy

DNA nanotechnology has attracted intense interest in biomedicine due to the advantages of good biocompatibility, structural programmability and multifunctionality. Herein, a DNA-Au nanomachine with active/passive dual-targeting capacity has been constructed, achieving lysosomal acidic microenvironment-activated combinational chemo-photothermal therapy of cervical carcinoma. The three-dimensional DNA nanoflowers (DNFs) are readily prepared via rolling circle amplification (RCA), in which the active targeting units (C-9S aptamers) for HeLa cells and drug-loading sites for doxorubicin (Dox) are rationally designed in the circular template. Meanwhile, the bovine serum albumin (BSA)-modified gold nanoparticles (BSA-AuNPs) with pH-responsive charge reversal ability are internalized into cancer cells through passive targeting mechanism of enhanced permeability and retention (EPR) effect. Under acidic stimuli (endosome and lysosome), the loaded Dox in DNFs is controllably released for targeted chemotherapy, and the charge of BSA-AuNPs is reversed from negative to positive in lysosome, resulting in the aggregation of BSA-AuNPs on DNFs through electrostatic interaction. Thus, hyperthermia is produced upon 808 nm laser irradiation for photothermal therapy (PTT). The in vitro and in vivo results demonstrate the highly chemo-photothermal therapy effect on cervical cancer based on the proposed DNA-Au nanomachine, providing a powerful and potential nanotheranostic platform for targeted combinational therapy of cancers in clinical applications.