Extracellular microparticles (MPs) can function as drug-delivery vehicles for anticancer drugs. Here, we show that the softness of MPs derived from tumour-repopulating cells (TRCs) isolated from three-dimensional fibrin gels enhances the MPs’ drug-delivery efficiency. We found that, compared with MPs derived from tumour cells cultured in conventional tissue-culture plastic, TRC-derived MPs intravenously injected in tumour-xenograft-bearing mice showed enhanced accumulation in tumour tissues, enhanced blood-vessel crossing and penetration into tumour parenchyma, and preferential uptake by highly tumorigenic TRCs. We also show that the cytoskeleton-related protein cytospin-A plays a critical role in the regulation of TRC-derived MP softness. The modulation of the mechanical properties of TRC-derived MPs could aid the efficiency of delivery of anticancer drugs.
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The data that support the findings of this study are available within the paper and its Supplementary Information files. Raw data are available from the corresponding authors upon reasonable request.
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We thank N. Wang from the Huazhong University of Science and Technology and University of Illinois at Urbana-Champaign for help in guiding and revising this manuscript. We thank Z. Zhang’s group from the Huazhong University of Science and Technology for help with the dorsal window chamber model. We thank the Analytical and Testing Center of the Huazhong University of Science and Technology and the Research Core Facilities for Life Science (HUST) for related analysis. This work was supported by the National Basic Research Program of China (2018YFA0208900 and 2015CB931802), National Natural Science Foundation of China (81627901, 81773653, 81672937, 81530080, 81788101 and 61572213) and Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2016-I2M-1–007).
The authors declare no competing interests.
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Liang, Q., Bie, N., Yong, T. et al. The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency. Nat Biomed Eng 3, 729–740 (2019). https://doi.org/10.1038/s41551-019-0405-4
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