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Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models

Author

Listed:
  • Myrofora Panagi

    (University of Cyprus)

  • Fotios Mpekris

    (University of Cyprus)

  • Pengwen Chen

    (The University of Tokyo)

  • Chrysovalantis Voutouri

    (University of Cyprus)

  • Yasuhiro Nakagawa

    (The University of Tokyo)

  • John D. Martin

    (The University of Tokyo)

  • Tetsuro Hiroi

    (National Cancer Center, Kashiwanoha
    The University of Tokyo, Kashiwanoha)

  • Hiroko Hashimoto

    (National Cancer Center, Kashiwanoha)

  • Philippos Demetriou

    (The Center for the Study of Hematological and other Malignancies)

  • Chryso Pierides

    (The Center for the Study of Hematological and other Malignancies)

  • Rekha Samuel

    (Christian Medical College Campus Bagayam)

  • Andreas Stylianou

    (University of Cyprus
    European University of Cyprus)

  • Christina Michael

    (University of Cyprus)

  • Shigeto Fukushima

    (The University of Tokyo)

  • Paraskevi Georgiou

    (European University of Cyprus)

  • Panagiotis Papageorgis

    (European University of Cyprus)

  • Petri Ch. Papaphilippou

    (University of Cyprus)

  • Laura Koumas

    (The Center for the Study of Hematological and other Malignancies
    Karaiskakio Foundation)

  • Paul Costeas

    (The Center for the Study of Hematological and other Malignancies
    Karaiskakio Foundation
    Cyprus Cancer Research Institute)

  • Genichiro Ishii

    (National Cancer Center, Kashiwanoha
    National Cancer Center Hospital East, Kashiwanoha)

  • Motohiro Kojima

    (National Cancer Center, Kashiwanoha)

  • Kazunori Kataoka

    (Kawasaki Institute of Industrial Promotion
    The University of Tokyo)

  • Horacio Cabral

    (The University of Tokyo)

  • Triantafyllos Stylianopoulos

    (University of Cyprus)

Abstract

Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.

Suggested Citation

  • Myrofora Panagi & Fotios Mpekris & Pengwen Chen & Chrysovalantis Voutouri & Yasuhiro Nakagawa & John D. Martin & Tetsuro Hiroi & Hiroko Hashimoto & Philippos Demetriou & Chryso Pierides & Rekha Samuel, 2022. "Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34744-1
    DOI: 10.1038/s41467-022-34744-1
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    References listed on IDEAS

    as
    1. Vikash P. Chauhan & John D. Martin & Hao Liu & Delphine A. Lacorre & Saloni R. Jain & Sergey V. Kozin & Triantafyllos Stylianopoulos & Ahmed S. Mousa & Xiaoxing Han & Pichet Adstamongkonkul & Zoran Po, 2013. "Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
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