Kateh Shamshiri Maryam, Vakili-Ghartavol Roghayyeh, Aiyelabegan Hammed Tanimowo, Asvar Zahra, Zare Marzouni Hadi, Matbou Riahi Maryam, Jaafari Mahmoud Reza
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
Cytokine. 2025 Mar;187:156860. doi: 10.1016/j.cyto.2025.156860. Epub 2025 Jan 11.
While liposomes enhance the safety and pharmacokinetic profile of free drugs, they have not significantly improved therapeutic efficacy. To overcome this challenge, targeted depletion of tumor-associated macrophages (TAMs) shows significant potential as an effective antitumor therapy, reducing off-target effects in comparison to non-targeted liposomes. In the context of peptide-mediated targeted cancer therapy, we evaluated the reprogramming activity of IFN-γ liposomes on TAMs, as well as that of IFN-γ liposomes modified with an M2 macrophage-targeting peptide, which binds preferentially to murine anti-inflammatory M2 macrophages/M2-like TAMs. Flow cytometry analysis showed significantly enhanced cellular uptake of m2-peptide-targeted liposomes in J774.1 macrophage cell lines compared to non-targeted liposomes. In BALB/c mice bearing C-26 murine carcinoma, the m2-peptide-targeted liposome groups exhibited significantly higher IFN-γ concentrations compared to non-targeted counterparts within the tumor environment. Furthermore, m2-peptide-targeted F2 liposomes at doses of 25 μg IFN-γ/kg resulted in superior tumor growth inhibition and greater tumor accumulation, indicating the potential of macrophage-targeted therapy in cancer growth inhibition. However, they failed to improve the overall therapeutic efficacy compared to Doxil. This study proposes a combination therapy of m2-peptide-targeted IFN-γ liposomes with successful chemotherapeutic liposomes such as Doxil.
虽然脂质体提高了游离药物的安全性和药代动力学特征，但它们并未显著提高治疗效果。为了克服这一挑战，靶向清除肿瘤相关巨噬细胞（TAM）作为一种有效的抗肿瘤治疗方法显示出巨大潜力，与非靶向脂质体相比，可减少脱靶效应。在肽介导的靶向癌症治疗背景下，我们评估了IFN-γ脂质体对TAM的重编程活性，以及用M2巨噬细胞靶向肽修饰的IFN-γ脂质体的重编程活性，该肽优先结合小鼠抗炎M2巨噬细胞/M2样TAM。流式细胞术分析显示，与非靶向脂质体相比，m2肽靶向脂质体在J774.1巨噬细胞系中的细胞摄取显著增强。在携带C-26小鼠癌的BALB/c小鼠中，与肿瘤环境中的非靶向对应物相比，m2肽靶向脂质体组的IFN-γ浓度显著更高。此外，剂量为25μg IFN-γ/kg的m2肽靶向F2脂质体导致了更好的肿瘤生长抑制和更大的肿瘤蓄积，表明巨噬细胞靶向治疗在抑制癌症生长方面的潜力。然而，与多柔比星脂质体相比，它们未能提高整体治疗效果。本研究提出了m2肽靶向IFN-γ脂质体与成功的化疗脂质体（如多柔比星脂质体）联合治疗的方案。
