使用 PCN-224@IrNCs/D-Arg 纳米平台重编程肿瘤微环境，以协同 PDT、NO 和放射增敏治疗乳腺癌并提高抗肿瘤免疫力,Nanoscale

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使用 PCN-224@IrNCs/D-Arg 纳米平台重编程肿瘤微环境，以协同 PDT、NO 和放射增敏治疗乳腺癌并提高抗肿瘤免疫力
Nanoscale ( IF 5.8 ) Pub Date : 2023-05-25 , DOI: 10.1039/d3nr01050c
Yi-Ming Zou ₁ , Rong-Tian Li ₁ , Lei Yu ₂ , Ting Huang ₁ , Jian Peng ₁ , Wei Meng ₁ , Bin Sun ₁ , Wen-Hua Zhang ₃ , Zhi-Hong Jiang ₄ , Jun Chen ₁ , Jin-Xiang Chen ₁

Affiliation

乳腺癌放射治疗（RT）过程中，肿瘤软组织X射线衰减系数低，肿瘤微环境（TME）缺氧，导致放射抵抗，从而降低治疗效果。此外，TME引起的免疫抑制严重限制了放射治疗的抗肿瘤免疫力。在本文中，我们提出了一种 PCN-224@IrNCs/ D -Arg 纳米平台，用于乳腺癌的协同放射增敏、光动力和 NO 治疗，同时增强抗肿瘤免疫力（PCN = 多孔协调网络，IrNCs = 铱纳米晶体，D -Arg = D-精氨酸）。可以通过以下方式选择性消融局部肿瘤：重新编程肿瘤微环境 (TME)、光动力疗法 (PDT) 和 NO 疗法，以及使放射疗法增敏的高 Z 元素 Ir 的存在。这些治疗方式的协同执行也导致了适应的抗肿瘤免疫反应。纳米平台的内在免疫调节作用还将巨噬细胞重新极化为 M1 表型并诱导树突状细胞成熟，激活抗肿瘤 T 细胞以诱导免疫原性细胞死亡，如体外和体内所证明的那样。本文报道的纳米复合材料设计代表了一种通过 TME 重编程治疗乳腺癌的新方案，以发挥有效癌症治疗和抗肿瘤免疫的协同作用。

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Reprogramming of the tumor microenvironment using a PCN-224@IrNCs/D-Arg nanoplatform for the synergistic PDT, NO, and radiosensitization therapy of breast cancer and improving anti-tumor immunity

The low X-ray attenuation coefficient of tumor soft tissue and the hypoxic tumor microenvironment (TME) during radiation therapy (RT) of breast cancer result in RT resistance and thus reduced therapeutic efficacy. In addition, immunosuppression induced by the TME severely limits the antitumor immunity of radiation therapy. In this paper, we propose a PCN-224@IrNCs/D-Arg nanoplatform for the synergistic radiosensitization, photodynamic, and NO therapy of breast cancer that also boosts antitumor immunity (PCN = porous coordination network, IrNCs = iridium nanocrystals, D-Arg = D-arginine). The local tumors can be selectively ablated via reprogramming the tumor microenvironment (TME), photodynamic therapy (PDT) and NO therapy, and the presence of the high-Z element Ir that sensitizes radiotherapy. The synergistic execution of these treatment modalities also resulted in adapted antitumor immune response. The intrinsic immunomodulatory effects of the nanoplatform also repolarize macrophages toward the M1 phenotype and induce dendritic cell maturation, activating antitumor T cells to induce immunogenic cell death as demonstrated in vitro and in vivo. The nanocomposite design reported herein represents a new regimen for the treatment of breast cancer through TME reprogramming to exert a synergistic effect for effective cancer therapy and antitumor immunity.

更新日期：2023-05-25

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