Persistent Luminescence Nanocarriers Functionalization with PD-1 Enriched Cell Membrane Enable in Vivo Tumor Targeting and Colorectal Cancer Chemo-Immunotherapy

Zhi‐hao Wang, Jingmin Liu, Feier Yang, Yaozhong Hu, Huan Lv, Shuo Wang
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引用次数: 2

Abstract

Colorectal cancer has become one of the malignant tumors with a high rate of morbidity and mortality. Therefore, how to effectively treat colorectal cancer is crucial. Although nano delivery system has been applied to the therapy of colorectal cancer, the majority of existing nano delivery systems still have drawbacks such as low biocompatibility and poor targeting ability. In this work, programmed cell death receptor 1 (PD-1) functionalized cell membrane bioinspired nanoplatform was prepared to enhance the targeting and therapeutic effect for colorectal cancer chemo-immunotherapy. Firstly, hollow long persistence luminescence nanomaterials were synthesized with superior background-free bioimaging effect and high drug-loading content. After loaded with cisplatin, the nanoplatform was camouflaged with erythrocyte and PD-1 expressed 293T hybrid cell membrane. In vivo animal imaging experiment showed that the nano delivery system camouflaged with hybrid cell membrane not only had excellent immune escape ability, but had excellent tumor active targeting ability. In vivo anticancer experiments showed that combined chemotherapy and immunotherapy of this nano delivery system could significantly inhibit tumor growth in tumor-bearing mice. In summary, the PD-1 protein-functionalized cell membrane camouflage produced excellent immune escape ability and cancer active targeting ability, providing a new modality for biomimetic nano delivery systems.
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具有PD-1富集细胞膜的持续发光纳米载体功能化实现体内肿瘤靶向和结直肠癌化学免疫治疗
结直肠癌已成为我国发病率和死亡率较高的恶性肿瘤之一。因此,如何有效治疗结直肠癌至关重要。虽然纳米递送系统已应用于结直肠癌的治疗,但现有的大多数纳米递送系统仍存在生物相容性低、靶向性差等缺点。本研究制备了程序性细胞死亡受体1 (PD-1)功能化的细胞膜生物激发纳米平台,以提高结直肠癌化疗免疫治疗的靶向性和治疗效果。首先,合成了具有良好的无背景生物成像效果和高载药量的空心长持久性发光纳米材料。负载顺铂后,纳米平台被红细胞和PD-1表达的293T杂交细胞膜伪装。体内动物成像实验表明,混合细胞膜伪装的纳米递送系统不仅具有良好的免疫逃逸能力,而且具有良好的肿瘤主动靶向能力。体内抗癌实验表明,该纳米递送系统联合化疗和免疫治疗可显著抑制荷瘤小鼠的肿瘤生长。综上所述,PD-1蛋白功能化的细胞膜伪装具有优异的免疫逃逸能力和肿瘤主动靶向能力,为仿生纳米递送系统提供了一种新的模式。
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