Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects. We utilized fullerenol as a "histone", packaged a great number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome" (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the encapsulation efficiency of Dox in the polymeric micelles was increased from similar to 5% to similar to 79%. What's more, the biomimetic-inspired delivery system significantly reduced the chemodrug side effects by utilizing the radical scavenging ability of fullerenol. This novel drug-delivery design approach provides useful insights for improving the applicability of fullerenol in drug delivery systems for cancer therapy. (C) 2018 Elsevier Ltd. All rights reserved.