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

  • Nanomedicine (Lond). 2019 Mar;14(5):613-626. doi: 10.2217/nnm-2018-0334.
Xiao Wei  1 ,  Rui Wei  1 ,  Guiying Jiang  1 ,  Yijuan Jia  2 ,  Hua Lou  1 ,  Zongyuan Yang  1 ,  Danfeng Luo  1 ,  Quanfu Huang  3 ,  Sen Xu  1 ,  Xin Yang  1 ,  Ying Zhou  1 ,  Xiaoting Li  1 ,  Teng Ji  1 ,  Junbo Hu  4 ,  Ling Xi  1 ,  Ding Ma  1 ,  Fei Ye  5 ,  Qinglei Gao  1
Affiliations
  • 1. Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
  • 2. Department of Obstetrics & Gynecology, Wuhan First Hospital, Wuhan, 430022, China.
  • 3. Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
  • 4. Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
  • 5. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
PMID: 30816057 DOI: 10.2217/nnm-2018-0334
Abstract

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.
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