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

Carrier-free nanomedicines mainly composed by nanocrystals of drug are considered as promising candidates for the next generation of nanodrug formulations. However, such nanomedicines still need to be stabilized by additive surfactants, synthetic polymers or biologically-based macromolecules. Contributed by 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 non-active excipients. In the assemblies of IDM and PTX (IDM/PTX assemblies), PTX nanocrystals are casted with amorphous IDM molecules like "brick-cements" architecture. In serum, these nanoassemblies could rapidly collapsed into a great number of smaller nanoparticles, thus targeting the tumor site through 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 non-active excipients might open an alternative avenue and give inspiration to fabricate novel carrier-free nanomedicines in many fields.