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Panagi, Myrofora; Mpekris, Fotios; Chen, Pengwen; Voutouri, Chrysovalantis; Nakagawa, Yasuhiro; Martin, John D; Hiroi, Tetsuro; Hashimoto, Hiroko; Demetriou, Philippos; Pierides, Chryso; Samuel, Rekha; Stylianou, Andreas; Michael, Christina; Fukushima, Shigeto; Georgiou, Paraskevi; Papageorgis, Panagiotis; Papaphilippou, Petri Ch; Koumas, Laura; Costeas, Paul; Ishii, Genichiro; Kojima, Motohiro; Kataoka, Kazunori; Cabral, Horacio; Stylianopoulos, Triantafyllos
Nature communications, 11/2022, Letnik: 13, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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