当前位置：
X-MOL 学术
›
Mol. Pharmaceutics
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Cadherin-17 Targeted Near-Infrared Photoimmunotherapy for Treatment of Gastrointestinal Cancer.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-09-15 , DOI: 10.1021/acs.molpharmaceut.0c00700 Yick-Liang Lum 1 , John M Luk 2 , Donald E Staunton 3 , Dennis K P Ng 4 , Wing-Ping Fong 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-09-15 , DOI: 10.1021/acs.molpharmaceut.0c00700 Yick-Liang Lum 1 , John M Luk 2 , Donald E Staunton 3 , Dennis K P Ng 4 , Wing-Ping Fong 1
Affiliation
|
In cancer photodynamic therapy (PDT), a photosensitizer taken up by cancer cells can generate reactive oxygen species upon near-infrared light activation to induce cancer cell death. To increase PDT potency and decrease its adverse effect, one approach is to conjugate the photosensitizer with an antibody that specifically targets cancer cells. In the present study, IR700, a hydrophilic phthalocyanine photosensitizer, was conjugated to the humanized monoclonal antibody ARB102, which binds specifically cadherin-17 (CDH17 aka CA17), a cell surface marker highly expressed in gastrointestinal cancer to produce ARB102-IR700. Photoimmunotherapy (PIT) of gastrointestinal cancer cell lines was conducted by ARB102-IR700 treatment and near-infrared light irradiation. The results showed that ARB102-IR700 PIT could induce cell death in CDH17-positive cancer cells with high potency. In a co-culture model, CDH17-negative and CDH17-overexpressing SW480 cells were labeled with distinct fluorescent dyes and cultured together prior to PIT treatment. The results confirmed that ARB102-IR700 PIT could kill CDH17-positive cells specifically, while leaving the adjacent CDH17-negative cells unaffected. An in vivo efficacy study was conducted using a pancreatic adenocarcinoma AsPC-1 xenograft tumor model in nude mice. Fluorescence scanning indicated that ARB102-IR700 accumulated specifically in the tumor sites. To perform PIT, at 24 and 48 h postinjection, mice were irradiated with a 680 nm laser at the tumor site to activate the photosensitizer. It was shown that ARB102-IR700 PIT could inhibit tumor growth significantly. In summary, this study demonstrated that the novel ARB102-IR700 is a promising agent for PIT in gastrointestinal cancers.
中文翻译：
Cadherin-17 靶向近红外光免疫疗法治疗胃肠癌。
在癌症光动力疗法 (PDT) 中，癌细胞吸收的光敏剂可以在近红外光激活时产生活性氧，从而诱导癌细胞死亡。为了提高 PDT 效力并减少其副作用，一种方法是将光敏剂与专门针对癌细胞的抗体结合。在本研究中，IR700（一种亲水性酞菁光敏剂）与人源化单克隆抗体 ARB102 结合，ARB102 特异性结合钙粘蛋白-17（CDH17 又名 CA17），这是一种在胃肠道癌中高度表达的细胞表面标志物，以产生 ARB102-IR700。通过ARB102-IR700处理和近红外光照射进行胃肠癌细胞系的光免疫疗法（PIT）。结果表明，ARB102-IR700 PIT可以高效诱导CDH17阳性癌细胞的细胞死亡。在共培养模型中，CDH17 阴性和 CDH17 过表达的 SW480 细胞用不同的荧光染料标记，并在 PIT 处理之前一起培养。结果证实ARB102-IR700 PIT可以特异性杀伤CDH17阳性细胞，同时不影响相邻的CDH17阴性细胞。一个在裸鼠中使用胰腺腺癌 AsPC-1 异种移植肿瘤模型进行体内功效研究。荧光扫描表明 ARB102-IR700 在肿瘤部位特异性积累。为了进行 PIT，在注射后 24 和 48 小时，小鼠在肿瘤部位用 680 nm 激光照射以激活光敏剂。结果表明，ARB102-IR700 PIT能显着抑制肿瘤生长。总之，这项研究表明，新型 ARB102-IR700 是一种很有前景的胃肠道癌症 PIT 药物。
更新日期：2020-10-05
中文翻译：
Cadherin-17 靶向近红外光免疫疗法治疗胃肠癌。
在癌症光动力疗法 (PDT) 中，癌细胞吸收的光敏剂可以在近红外光激活时产生活性氧，从而诱导癌细胞死亡。为了提高 PDT 效力并减少其副作用，一种方法是将光敏剂与专门针对癌细胞的抗体结合。在本研究中，IR700（一种亲水性酞菁光敏剂）与人源化单克隆抗体 ARB102 结合，ARB102 特异性结合钙粘蛋白-17（CDH17 又名 CA17），这是一种在胃肠道癌中高度表达的细胞表面标志物，以产生 ARB102-IR700。通过ARB102-IR700处理和近红外光照射进行胃肠癌细胞系的光免疫疗法（PIT）。结果表明，ARB102-IR700 PIT可以高效诱导CDH17阳性癌细胞的细胞死亡。在共培养模型中，CDH17 阴性和 CDH17 过表达的 SW480 细胞用不同的荧光染料标记，并在 PIT 处理之前一起培养。结果证实ARB102-IR700 PIT可以特异性杀伤CDH17阳性细胞，同时不影响相邻的CDH17阴性细胞。一个在裸鼠中使用胰腺腺癌 AsPC-1 异种移植肿瘤模型进行体内功效研究。荧光扫描表明 ARB102-IR700 在肿瘤部位特异性积累。为了进行 PIT，在注射后 24 和 48 小时，小鼠在肿瘤部位用 680 nm 激光照射以激活光敏剂。结果表明，ARB102-IR700 PIT能显着抑制肿瘤生长。总之，这项研究表明，新型 ARB102-IR700 是一种很有前景的胃肠道癌症 PIT 药物。
京公网安备 11010802027423号