Royal College of Surgeons in Ireland
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A nanoscale shape-discovery framework supporting systematic investigations of shape-dependent biological effects and immunomodulation

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journal contribution
posted on 2023-05-16, 14:29 authored by Wei Zhang, Hender Lopez, Luca Boselli, Paolo Bigini, André Perez-Potti, Zengchun Xie, Valentina Castagnola, Qi Cai, Camila P Silveira, Joao M de Araujo, Laura Talamini, Nicolò Panini, Giuseppe Ristagno, Martina B Violatto, Stéphanie Devineau, Marco MonopoliMarco Monopoli, Mario Salmona, Valeria A Giannone, Sandra Lara, Kenneth A Dawson, Yan Yan
Since it is now possible to make, in a controlled fashion, an almost unlimited variety of nanostructure shapes, it is of increasing interest to understand the forms of biological control that nanoscale shape allows. However, a priori rational investigation of such a vast universe of shapes appears to present intractable fundamental and practical challenges. This has limited the useful systematic investigation of their biological interactions and the development of innovative nanoscale shape-dependent therapies. Here, we introduce a concept of biologically relevant inductive nanoscale shape discovery and evaluation that is ideally suited to, and will ultimately become, a vehicle for machine learning discovery. Combining the reproducibility and tunability of microfluidic flow nanochemistry syntheses, quantitative computational shape analysis, and iterative feedback from biological responses in vitro and in vivo, we show that these challenges can be mastered, allowing shape biology to be explored within accepted scientific and biomedical research paradigms. Early applications identify significant forms of shape-induced biological and adjuvant-like immunological control.


Science Foundation Ireland (15/SIRG/3423, 16/ENM-ERA/3457, 17/NSFC/4898)

Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment (2019KSYS008)

Irish Research Council (EPSPD/ 2015/5, GOIPD/2016/128, GOIPG/2014/874)

Chinese Scholarship Council (Agreement Nos. 201706220062, 201806220054, and 201408300003)



The original article is available at

Published Citation

Zhang W, et al. A nanoscale shape-discovery framework supporting systematic investigations of shape-dependent biological effects and immunomodulation. ACS Nano. 2021;16(1):1547-1559.

Publication Date

27 December 2021

PubMed ID



  • Chemistry

Research Area

  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine


American Chemical Society (ACS)


  • Published Version (Version of Record)