Mechano-boosting nanomedicine antitumour efficacy by blocking the reticuloendothelial system with stiff nanogels

Zheng Li, Yabo Zhu, Haowen Zeng, Chong Wang, Chen Xu, Qiang Wang, Huimin Wang, Shiyou Li, Jitang Chen, Chen Xiao, Xiangliang Yang and Zifu Li ()
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Zheng Li: Huazhong University of Science and Technology
Yabo Zhu: Huazhong University of Science and Technology
Haowen Zeng: Huazhong University of Science and Technology
Chong Wang: Huazhong University of Science and Technology
Chen Xu: Huazhong University of Science and Technology
Qiang Wang: Huazhong University of Science and Technology
Huimin Wang: Huazhong University of Science and Technology
Shiyou Li: Huazhong University of Science and Technology
Jitang Chen: Huazhong University of Science and Technology
Chen Xiao: Huazhong University of Science and Technology
Xiangliang Yang: Huazhong University of Science and Technology
Zifu Li: Huazhong University of Science and Technology

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Nanomedicine has been developed for cancer therapy over several decades, while rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits nanomedicine antitumour efficacy. We design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES. Stiff nanogels are injected preferentially to abrogate uptake capacity of macrophages and temporarily block RES, relying on inhibition of clathrin and prolonged liver retention. Afterwards, soft nanogels deliver doxorubicin (DOX) with excellent efficiency, reflected in high tumour accumulation, deep tumour penetration and outstanding antitumour efficacy. In this work, we combine the advantage of stiff nanogels in RES-blockade with the superiority of soft nanogels in drug delivery leads to the optimum tumour inhibition effect, which is defined as mechano-boosting antitumour strategy. Clinical implications of stiffness-dependent RES-blockade are also confirmed by promoting antitumour efficacy of commercialized nanomedicines, such as Doxil and Abraxane.

Date: 2023
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DOI: 10.1038/s41467-023-37150-3

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