Supramolecularly self-assembled nano-twin drug for reversing multidrug resistance

Abstract

Multidrug resistance (MDR) is one of the most important reasons for the failure of clinical chemotherapy treatment of cancer patients. Although several strategies have been proposed to overcome MDR, their contributions in improving therapeutic efficacy are not adequate. Herein, we constructed a nano-twindrug using a supramolecular self-assembling strategy, with the aim of efficiently reversing MDR. Due to the supramolecular interactions, doxorubicin (DOX) and vorinostat (SAHA) could self-assemble into stable spherical nanoparticles with a size of ∼160 nm. Since the antitumor drugs were not modified by nontherapeutic drug carriers, our strategy ensured a drug-loading efficacy of 100%. Furthermore, our study revealed that the DOX-SAHA nano-twin drug could enter drug-resistant cancer cells and inhibit their proliferation more effectively in vitro than single DOX, SAHA, or a DOX/SAHA mixture. In the meantime, the DOX-SAHA nano-twin drug could accumulate at the tumor site in vivo and show higher antitumor efficacy accompanied by low side effects.