4.8 Article

Tuning the Elasticity of Nanogels Improves Their Circulation Time by Evading Immune Cells

期刊

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202116653

关键词

Biodistribution; Elasticity; Nanogels; Phagocytosis; Radiolabeling

资金

  1. Deutsche Forschungsgemeinschaft (DFG) [331065168, SFB 985]
  2. Russian Science Foundation [21-73-30013]
  3. Projekt DEAL
  4. Russian Science Foundation [21-73-30013] Funding Source: Russian Science Foundation

向作者/读者索取更多资源

This study demonstrates that by tuning the mechanical properties of nanogels, significant enhancement in their circulation time can be achieved, leading to improved radiation damage to tumor cells. The results show that small changes in the mechanical properties of nanogels influence their fate inside cells, which is confirmed by PET/CT and computer simulations.
Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro- and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano- or microgels.

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