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肺癌的靶向诊疗:基于程序性死亡受体配体1(PD-L1)引导的载有叶绿素e6的金纳米棱晶递送,用于增强成像及光热/光动力治疗

Targeted theranostics of lung cancer: PD-L1-guided delivery of gold nanoprisms with chlorin e6 for enhanced imaging and photothermal/photodynamic therapy.

作者信息

Liu Bin, Qiao Guanglei, Han Yu, Shen E, Alfranca Gabriel, Tan Haisong, Wang Lirui, Pan Shaojun, Ma Lijun, Xiong Wujun, Liu Yanlei, Cui Daxiang

机构信息

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China; National Engineering Center for Nanotechnology, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xian Xia Road, Shanghai 200336, China.

出版信息

Acta Biomater. 2020 Nov;117:361-373. doi: 10.1016/j.actbio.2020.09.040. Epub 2020 Sep 29.

Abstract

Peptide modified nanoparticles have emerged as powerful tools for enhanced cancer diagnosis and novel treatment strategies. Here, human programmed death-ligand 1 (PD-L1) peptides were used for the first time for the modification of gold nanoprisms (GNPs) to enhance targeting efficiency. A multifunctional nanoprobe was developed that the GNPs@PEG/Ce6-PD-L1 peptide (GNPs@PEG/Ce6-P) was used for imaging-guided photothermal/photodynamic therapy by using the targeting effect of PD-L1. Both confocal imaging and flow cytometry experiments demonstrated a remarkable affinity of the as-prepared nanoprobes GNPs@PEG/Ce6-P to lung cancer cells (HCC827), which have a high PD-L1 expression. Subsequent in vitro and in vivo experiments further demonstrated that the nanoprobes GNPs@PEG/Ce6-P not only allowed for real-time visualization via fluorescence (FL) imaging and photoacoustic (PA) imaging, but also served as phototherapy agents for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, treatments on human lung cancer cells-derived tumors demonstrated that the nanoprobes GNPs@PEG/Ce6-P could significantly suppress tumor growth through PTT and PDT from GNPs and Ce6, respectively. In conclusion, the as-prepared new nanoprobes show promising potential for nanomedicine with remarkable targeting ability for dual-mode imaging and enhanced PDT and PTT effects on lung cancer.

摘要

肽修饰的纳米颗粒已成为增强癌症诊断和新型治疗策略的有力工具。在此,首次使用人程序性死亡配体1(PD-L1)肽修饰金纳米棱柱状颗粒(GNPs)以提高靶向效率。开发了一种多功能纳米探针,即GNPs@PEG/Ce6-PD-L1肽(GNPs@PEG/Ce6-P),利用PD-L1的靶向作用用于成像引导的光热/光动力治疗。共聚焦成像和流式细胞术实验均表明,所制备的纳米探针GNPs@PEG/Ce6-P对高表达PD-L1的肺癌细胞(HCC827)具有显著的亲和力。随后的体外和体内实验进一步证明,纳米探针GNPs@PEG/Ce6-P不仅能够通过荧光(FL)成像和光声(PA)成像实现实时可视化,还可作为光疗剂用于协同光热治疗(PTT)和光动力治疗(PDT)。此外,对人肺癌细胞衍生肿瘤的治疗表明,纳米探针GNPs@PEG/Ce6-P可分别通过GNPs和Ce6的PTT和PDT显著抑制肿瘤生长。总之,所制备的新型纳米探针在纳米医学方面显示出有前景的潜力,对肺癌具有显著的靶向能力,可实现双模态成像以及增强的PDT和PTT效果。

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