Regulating nanogel mechanics to boost drug delivery and antitumor efficacy

Introduction: The mechanical properties of nanomedicines have received tremendous attention in recent years, but the mechanism by which the mechanical properties of nanomedicines affect antitumor effects is not yet clear [1-2].

Materials & Methods: We leveraged nanogels of different mechanical properties as model nanomedicines to uncover the impacts of nanomedicine mechanical properties on drug delivery and antitumor efficacy.

Results & Discussion: We found that compared with stiff nanogel, soft nanogel presented higher cellular uptake [3-4]. At the same time, nanogels with different stiffness showed significant distribution differences in varied tissues and organs. Thanks to the excellent deformability, soft nanogel can overcome tumor's dense extracellular matrix, achieve higher tumor concentration, deeper penetration and stronger antitumor effect relative to stiff counterparts. We further elucidated that the mechanical properties of blocking materials were a key parameter affecting the blocking strategy of the reticuloendothelial system. Therefore, prior injection of stiff nanogels can inhibit the clatherin-mediated endocytosis of macrophages and prolong the retention time in the liver, which can abrogate the endocytosis ability of macrophages and temporarily block the reticuloendothelial system.

Conclusions: Our study corroborates that the mechanical properties are an essential factor that profoundly affects the delivery efficiency of nanomedicines.

References

1. Li Zheng, et al. Soc. Rev. 2020, 49, 2273-2290.
2. Li Zheng, et al. Mater. 2024, 36, 1041-1053.
3. Li Zheng, et al. Nature Communications 2023, 14, 1437.
4. Li Zheng, et al. Sci. 2024, 11, 2306730.