R11 peptides can promote the molecular imaging of spherical nucleic acids for bladder cancer margin identification

R11 peptides can promote the molecular imaging of spherical nucleic acids for bladder cancer margin identification
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R11肽可促进球形核酸分子成像用于膀胱癌边缘识别

DOI:
10.1007/s12274-021-3807-z
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发表时间:
2021-09
期刊:
影响因子:
9.9
通讯作者:
Fan Jinhai
Fan Jinhai
中科院分区:
材料科学1区
文献类型:
--
作者:
Ma Minghai;Zhang Pu;Liang Xiao;Cui Daxiang;Shao Qiuya;Zhang Haibao;Zhang Mengzhao;Yang Tao;Wang Lu;Zhang Nan;Jing Minxuan;Zhang Lu;Dan Weichao;Song Rundong;Liu Xi;Hao Jiatao;Chen Yuhang;Gu Lijiang;Wang Lei;Fan Jinhai

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膀胱癌(BC)治疗的关键问题之一是疾病的局部复发。然而,由于缺乏有效的肿瘤边缘识别技术,术中实现肿瘤边缘的准确勾画仍然极其困难。在此,生存素分子信标(MB)和R11肽连接的球形核酸(SNA)被合成为纳米探针(AuNP-MB@R11),用于BC边缘的灵敏检测。理化性质证明R11肽和生存素MB成功负载到SNA表面。 AuNP-MB@R11对核酸酶活性具有良好的稳定性,并且在体外检测生存素单链DNA(ssDNA)时具有高灵敏度和特异性。根据细胞学,R11肽可以增加SNA的BC靶向能力和膜穿透性。值得注意的是,R11 肽显着促进溶酶体的崩解和 SNA 的释放,从而提高荧光成像质量。进一步的RNA测序证明,一些与内吞作用和溶酶体相关的基因和通路受到显着调控,如AGPAT5、GPD1L和GRB2。在原位 BC 模型和 BC 患者的临床样本中,AuNP-MB@R11 显示出更清晰的癌性荧光边缘,与 SNA 相比,检测效果显着改善。 R11肽连接的SNA在识别BC边缘方面具有广阔的前景,这可能有助于提高手术中的R0切除率并改善患者的生活质量。
One of the critical problems in bladder cancer (BC) management is the local recurrence of disease. However, achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition technology. Herein, survivin molecular beacon (MB) and R11 peptide-linked spherical nucleic acids (SNAs) were synthesized as nanoprobes (AuNP-MB@R11) for sensitive detection of BC margins. Physicochemical properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of SNAs. AuNP-MB@R11 had good stability against nuclease activity and high sensitivity and specificity to detect survivin single strand DNA (ssDNA)in vitro. According to cytology, R11 peptides could increase the BC targeting ability and membrane penetrability of SNAs. Notably, R11 peptides significantly promoted the disintegration of lysosomes and the release of SNAs to enhance fluorescence imaging quality. Further RNA sequencing proved that some genes and pathways related to endocytosis and lysosomes were significantly regulated, such as AGPAT5, GPD1L, and GRB2. In orthotopic BC models and a clinical sample from a patient with BC, AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection compared to those achieved by SNAs. R11 peptide-linked SNAs present promising potential to identify BC margin, which may help to improve the R0 resection rate in surgery and improve patients’ quality of life.
含有 siRNA 的铁掺杂温石棉纳米管可沉默 SPAG5 以治疗膀胱癌
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