Polymersomes-mediated delivery of CSF1R inhibitor to tumor associated macrophages promotes M2 to M1-like macrophage repolarization

Manuel Rodriguez-Perdigon, Sètuhn Jimaja, Laetitia Haen, Nico Bruns, Barbara Rothen-Rutishauser, Curzio Rüegg

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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Abstract

The crosstalk between cancer cells and tumor associated macrophages (TAMs) within the tumor environment modulates tumor progression at all stages of cancer disease. TAMs are predominantly M2-like polarized macrophages with tumor-promoting activities. Nonetheless, they can be repolarized to tumoricidal M1-like macrophages through macrophage colony stimulating factor 1 receptor inhibition (CSF1Ri). CSF1Ri is being explored as multifaced therapeutic approach to suppress TAMs tumor-promoting functions and reduce cancer cell aggressiveness and viability. However, treatment with CSF1Ri results in significant TAMs death, thereby extinguishing the possibility of generating tumoricidal M1-like macrophages. Immunotherapy has not only improved overall patient's survival in some cancer types, but also caused frequent off-target toxicity. Approaches to balance efficacy versus toxicity are needed. Herein, a CSF1Ri-loaded polymersomes (PMs) based delivery platform is developed to promote M2-like macrophage repolarization. When testing in vitro on primary human monocyte-derived macrophages (MDMs), CSF1Ri-loaded PMs are preferentially taken up by M2-like macrophages and enhance M2 to M1-like macrophage repolarization while minimizing cytotoxicity in comparison to the free drug. When testing in a MDMs-MDA-MB-231 breast cancer cell coculture model, CSF1Ri-loaded PMs further retain their M2 to M1-like macrophages polarization capacity. This CSF1Ri-loaded PM-based platform system represents a promising tool for macrophage-based immunotherapy approaches.

Original languageEnglish
Article number2200168
JournalMacromolecular Bioscience
Volume22
Issue number8
Early online date27 May 2022
DOIs
Publication statusPublished - 31 Aug 2022

Keywords

  • triple negative breast cancer
  • polymersomes
  • block copolymer vesicles
  • immunotherapies
  • tumor associated macrophages
  • drug delivery systems

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