A tumor-penetrable drug nanococktail made from human histones for interventional nucleus-targeted chemophotothermal therapy of drug-resistant tumors

ABSTRACT: Nanoparticle-based chemophotothermal therapy (CPT) is a promising treatment for multidrug resistant tumors. In this study, a drug nanococktail of DIR825@histone was developed by employing doxorubicin (DOX), NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser. After localized intervention, DIR825@histone penetrated tumor tissues by transcytosis, efficiently entered tumor cells and targeted the cell nuclei. DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release. Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting. Moreover, an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury. Therefore, DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors. Graphical abstract Image 1 Highlights • Proposing an interventional nucleus-targeted chemophotothermal therapy (CPT) for treating MDR tumors• Using natural human histones for the first time to fabricate nucleus-targeted nanococktails.• The nanococktail can penetrate tumor tissues by transcytosis, efficiently enter tumor cells and target the cell nuclei.• Highly improved intracellular MDR reversion and less heat shock response in drug-resistant tumor cells can be achieved by nucleus-targeted chemophotothermal therapy.• The combination of the nucleus-targeted DIR825@histone and interventional laser harvested the best therapeutic outcomes against drug-resistant tumor.

SUBMITTER: Guo J 

PROVIDER: S-EPMC8591402 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature