Facile Engineering of Indomethacin-Induced Paclitaxel Nanocrystal Aggregates as Carrier-Free Nanomedicine with Improved Synergetic Antitumor Activity

Abstract

Carrier-free nanomedicines mainly composed of drug nanocrystals are considered as promising candidates for next-generation nanodrug formulations. However, such nanomedicines still need to be stabilized by additive surfactants, synthetic polymers, or biologically based macromolecules. Based on the strong intermolecular interactions between indomethacin (IDM, a COX-2 inhibitor) and paclitaxel (PTX, a chemotherapy drug), we herein successfully engineered a novel kind of carrier-free nanomedicines that organized as IDM-induced PTX nanocrystal aggregates via one-pot self-assembly without any nonactive excipients. In the assemblies of IDM and PTX (IDM/PTX assemblies), PTX nanocrystals were casted with amorphous IDM molecules, like a "brick-cement" architecture. In serum, these nanoassemblies could rapidly collapse into a great number of smaller nanoparticles, thus targeting the tumor site through the EPR effect. Under the assistance of IDM on immunotherapy, the IDM/PTX assemblies showed obviously improved synergetic antitumor effects of immunotherapy and chemotherapy. The self-assembly of two synergistic active substances into nanomedicines without any nonactive excipients might open an alternative avenue and give inspiration to fabricate novel carrier-free nanomedicines in many fields.