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Mechanical cues modulate cellular uptake of nanoparticles in cancer via clathrin-mediated and caveolae-mediated endocytosis pathways

Xiao Wei,Rui Wei,Guiying Jiang,Yijuan Jia,Hua Lou,Zongyuan Yang,Danfeng Luo,Quanfu Huang,Sen Xu,Xin Yang,Ying Zhou,Xiaoting Li,Teng Ji,Junbo Hu,Ling Xi,Ding Ma,Fei Ye,Qinglei Gao

Aim: To investigate the influence of tissue mechanics on the cellular uptake efficiency of nanoparticles (NPs) in cancer. Materials & methods: Collagen-coated polyacrylamide gels were prepared as model substrates. Coumarin 6-loaded poly(lactic-co-glycolic) acid micelles (C6-NPs) were prepared to investigate the cellular uptake of NPs. Results: We demonstrated that substrate stiffness modulated the cellular uptake of NPs of cancer. Mechanistically, mechanical cues exerted influence on the clathrin-mediated endocytosis and caveolae-mediated endocytosis pathways, which mediated stiffness-regulated cellular uptake of NPs. Conclusion: Our findings shed light on the regulatory role of the mechanical cues on the cellular uptake of NPs and will facilitate the selection of clinical patients who might benefit from a given nanotherapy.