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

Zhang, Chengyuan, Long, Ling, Xiong, Yao, Wang, Chenping, Peng, Cuiping, Yuan, Yuchuan, Liu, Zhirui, Lin, Yongyao, Jia, Yi, Zhou, Xing, Li, Xiaohui
ACS applied materials & interfaces 2019 v.11 no.10 pp. 9872-9883
active ingredients, antineoplastic activity, blood serum, chemical interactions, drug therapy, engineering, immunotherapy, indomethacin, nanocrystals, nanomedicine, nanoparticles, neoplasms, paclitaxel, polymers, surfactants
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.