Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy

Ninad Kumbhojkar; Supriya Prakash; Tatsuya Fukuta; Kwasi Adu-Berchie; Neha Kapate; Rocky An; Solomina Darko; Vineeth Chandran Suja; Kyung Soo Park; Alexander P Gottlieb; Michael Griffith Bibbey; Malini Mukherji; Lily Li-Wen Wang; David J Mooney; Samir Mitragotri

doi:10.1038/s41551-024-01180-z

Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy

Nat Biomed Eng. 2024 Feb 29. doi: 10.1038/s41551-024-01180-z. Online ahead of print.

Authors

Ninad Kumbhojkar^{1

2}, Supriya Prakash^{1

2}, Tatsuya Fukuta^{1

2

3}, Kwasi Adu-Berchie², Neha Kapate^{1

2

4}, Rocky An^{1

5}, Solomina Darko¹, Vineeth Chandran Suja^{1

2}, Kyung Soo Park^{1

2}, Alexander P Gottlieb^{1

2

6}, Michael Griffith Bibbey^{1

2}, Malini Mukherji², Lily Li-Wen Wang^{1

2

4}, David J Mooney^{1

2}, Samir Mitragotri^{7

8}

Affiliations

¹ Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA, USA.
² Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
³ Department of Physical Pharmaceutics, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
⁴ Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁶ Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
⁷ Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, MA, USA. mitragotri@seas.harvard.edu.
⁸ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. mitragotri@seas.harvard.edu.

PMID: 38424352
DOI: 10.1038/s41551-024-01180-z

Abstract

Tumour-associated neutrophils can exert antitumour effects but can also assume a pro-tumoural phenotype in the immunosuppressive tumour microenvironment. Here we show that neutrophils can be polarized towards the antitumour phenotype by discoidal polymer micrometric 'patches' that adhere to the neutrophils' surfaces without being internalized. Intravenously administered micropatch-loaded neutrophils accumulated in the spleen and in tumour-draining lymph nodes, and activated splenic natural killer cells and T cells, increasing the accumulation of dendritic cells and natural killer cells. In mice bearing subcutaneous B16F10 tumours or orthotopic 4T1 tumours, intravenous injection of the micropatch-loaded neutrophils led to robust systemic immune responses, a reduction in tumour burden and improvements in survival rates. Micropatch-activated neutrophils combined with the checkpoint inhibitor anti-cytotoxic T-lymphocyte-associated protein 4 resulted in strong inhibition of the growth of B16F10 tumours, and in complete tumour regression in one-third of the treated mice. Micropatch-loaded neutrophils could provide a potent, scalable and drug-free approach for neutrophil-based cancer immunotherapy.

Abstract

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