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Biomimetic Nanoparticles Carrying a Repolarization Agent of Tumor-Associated Macrophages for Remodeling of the Inflammatory Microenvironment Following Photothermal Therapy
ACS Nano ( IF 17.1 ) Pub Date : 2021-09-01 , DOI: 10.1021/acsnano.1c05618
Yale Yue 1, 2, 3 , Fenfen Li 1, 2 , Yao Li 2 , Yazhou Wang 4 , Xinjing Guo 2 , Zhaoxia Cheng 2 , Nan Li 2 , Xiaotu Ma 2 , Guangjun Nie 2, 3, 5, 6 , Xiao Zhao 2, 5, 7
Affiliation  

The complete regression of residual tumors after photothermal therapy (PTT) depends on the activation and recognition of the immune system. However, the inevitable local inflammation after PTT in residual tumor recruits abundant abnormal immune cells, especially the tumor-associated macrophages (TAMs) which further promote immune escape and survival of the remaining tumor cells, resulting in the tumor recurrence and progression. To solve this problem, herein we explored biomimetic nanoparticles carrying repolarization agent of TAMs to remodel the post-PTT inflammatory microenvironment. The polydopamine nanoparticles were used simultaneously as photothermal transduction agents to ablate tumor cells and the delivery vehicles for TMP195 which can repolarize the M2-like TAMs into an antitumor phenotype. In addition, a biomimetic decoration of macrophage membrane coating was designed to endow nanoparticles the ability to actively target the tumor site after PTT mediated by inflammation-mediated chemotaxis. In the breast tumor model, these biomimetic nanoparticles with immune-modulating ability significantly elevated the levels of M1-like TAMs, ultimately resulting in a tumor-elimination rate of 60%, increased from 10% after PTT. This synergistic treatment strategy of PTT and TAMs repolarization provides a promising approach to address the deteriorated tumor microenvironment after PTT and proposes a more effective way for combinational treatment option in clinic.

中文翻译:

携带肿瘤相关巨噬细胞复极化剂的仿生纳米颗粒用于光热治疗后炎症微环境的重塑

光热疗法(PTT)后残留肿瘤的完全消退取决于免疫系统的激活和识别。然而,残留肿瘤PTT后不可避免的局部炎症会招募大量异常免疫细胞,尤其是肿瘤相关巨噬细胞(TAMs),进一步促进残留肿瘤细胞的免疫逃逸和存活,导致肿瘤复发和进展。为了解决这个问题,我们在此探索了携带 TAM 复极化剂的仿生纳米颗粒,以重塑 PTT 后的炎症微环境。聚多巴胺纳米颗粒同时用作消融肿瘤细胞的光热转导剂和 TMP195 的递送载体,TMP195 可以将 M2 样 TAM 重新极化为抗肿瘤表型。此外,巨噬细胞膜涂层的仿生装饰旨在赋予纳米粒子在炎症介导的趋化性介导的 PTT 后主动靶向肿瘤部位的能力。在乳腺肿瘤模型中,这些具有免疫调节能力的仿生纳米粒子显着提高了 M1 样 TAM 的水平,最终导致肿瘤消除率从 PTT 后的 10% 提高到 60%。这种PTT和TAMs复极化的协同治疗策略为解决PTT后恶化的肿瘤微环境提供了一种有前景的方法,并为临床上的联合治疗选择提供了一种更有效的方法。这些具有免疫调节能力的仿生纳米粒子显着提高了 M1 样 TAM 的水平,最终导致肿瘤消除率从 PTT 后的 10% 提高到 60%。这种PTT和TAMs复极化的协同治疗策略为解决PTT后恶化的肿瘤微环境提供了一种有前景的方法,并为临床上的联合治疗选择提供了一种更有效的方法。这些具有免疫调节能力的仿生纳米粒子显着提高了 M1 样 TAM 的水平,最终导致肿瘤消除率从 PTT 后的 10% 提高到 60%。这种PTT和TAMs复极化的协同治疗策略为解决PTT后恶化的肿瘤微环境提供了一种有前景的方法,并为临床上的联合治疗选择提供了一种更有效的方法。
更新日期:2021-09-28
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