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

Author:
Zhang, Chengyuan, Long, Ling, Xiong, Yao, Wang, Chenping, Peng, Cuiping, Yuan, Yuchuan, Liu, Zhirui, Lin, Yongyao, Jia, Yi, Zhou, Xing, Li, Xiaohui
Source:
ACS applied materials & interfaces 2019 v.11 no.10 pp. 9872-9883
ISSN:
1944-8252
Subject:
active ingredients, antineoplastic activity, blood serum, chemical interactions, drug therapy, engineering, immunotherapy, indomethacin, nanocrystals, nanomedicine, nanoparticles, neoplasms, paclitaxel, polymers, surfactants
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.
Agid:
6323715