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The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency

An Author Correction to this article was published on 08 February 2021

This article has been updated

Abstract

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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Fig. 1: Characterization of DOX@3D-MPs.
Fig. 2: Antitumour activity of drug-packaging 3D-MPs.
Fig. 3: Efficient tumour accumulation, extravasation and penetration of DOX@3D-MPs.
Fig. 4: Role of softness on the in vivo transport process of 3D-MPs.
Fig. 5: Involvement of cytospin-A in the regulation of softness and in vivo transport process of 3D-MPs.
Fig. 6: Involvement of cytospin-A in regulation of the anticancer activity of DOX-loaded MPs.

Data availability

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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Acknowledgements

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).

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Q.L., N.B., L.G., B.H. and X.Y. conceived and designed the experiments. Q.L., N.B., T.Y., K.T., Z.W., X.Z., H.Z. and W.H. performed the experiments. Q.L., N.B., T.Y., X.S., H.J., L.G., B.H. and X.Y. collected and analysed the data. L.G., B.H. and X.Y. supervised the project. L.G., B.H., X.Y. Q.L., N.B. and T.Y. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Lu Gan or Bo Huang or Xiangliang Yang.

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Supplementary Dataset 1

The upregulated proteins in 3D-MPs versus 2D-MPs.

Supplementary Dataset 2

The downregulated proteins in 3D-MPs versus 2D-MPs.

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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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