DNA decorated Cu9S5 nanoparticles as NIR light responsive drug carriers for tumor chemo–phototherapy

Abstract

Recently, near-infrared (NIR) light responsive drug delivery systems have attracted much attention for tumor therapy. Herein, we have successfully constructed a smart nanocarrier system Cu₉S₅-PEI–DNA-DOX (labelled as CPD–DOX) based on the self-assembly of hydrophobic Cu₉S₅ nanoparticles (NPs), poly(ethylene imine) (PEI), double-stranded DNA (dsDNA) segments and the anti-cancer drug doxorubicin (DOX). Among them, Cu₉S₅ NPs can serve as a nano-transducer for absorbing and converting near-infrared light to heat. Then, the hydrophobic layer of Cu₉S₅ NPs is coated with the dendritic polymer PEI through a simple approach. According to the temperature of the tumor tissue and the photothermal effect of Cu₉S₅ NPs, we specially designed a DNA sequence with a suitable melting temperature for NIR-light-promoted denaturation of DNA helices and drug release when DOX intercalated into the dsDNA through noncovalent interaction. Notably, the DOX-loaded dsDNA can be decorated on the surface of Cu₉S₅ NPs by convenient electrostatic adsorption rather than chemical bonding. The experimental results show that dsDNA can maintain a stable helical structure under physiological conditions but unzip the helix to release DOX upon NIR irradiation. Therefore, DOX can be safely delivered and released into cancer cells to exert anticancer effects. Based on in vitro cell cytotoxicity experiments, the CPD–DOX system has a synergistic effect for cancer cell apoptosis or death because of both the cytotoxicity of light-triggered DOX release and the Cu₉S₅-NP-mediated photothermal ablation effect. It is expected that the facile synthesis and low cost nanocarrier can improve the anticancer effect in contrast to the single chemotherapy or photothermal therapy mode.