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.
Keywords: cancer; cellular uptake; endocytic pathways; matrix stiffness; nanoparticle.