• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

表皮生长因子受体靶向西妥昔单抗-缬氨酸-瓜氨酸（vc）-阿霉素免疫偶联物-负载牛血清白蛋白（BSA）纳米颗粒用于结直肠肿瘤治疗。

EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy.

机构信息

Department of Pharmaceutics, State Key Laboratory of Nature Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.

Jiangsu Health Vocational College, Nanjing, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Mar 26;16:2443-2459. doi: 10.2147/IJN.S289228. eCollection 2021.

DOI:10.2147/IJN.S289228
PMID:33814909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8009551/
Abstract

BACKGROUND

Specific modifications to carriers to achieve targeted delivery of chemotherapeutics into malignant tissues are a critical point for efficient diagnosis and therapy. In this case, bovine serum albumin (BSA) was conjugated with cetuximab-valine-citrulline (vc)-doxorubicin (DOX) to target epidermal growth factor receptor (EGFR) and enable the release of drug in EGFR-overexpressed tumor cells.

METHODS

Maleimidocaproyl-valine-citrulline-p-aminobenzylcarbonyl-p-nitrophenol (MC-Val-Cit-PAB-PNP) and DOX were used to synthesize MC-Val-Cit-PAB-DOX, which was further linked with cetuximab to prepare antibody-drug conjugates (ADCs). Then, the ADCs were adsorbed to the surface of the BSA nanoparticles (NPs), which were prepared by a desolvation method to obtain cetuximab-vc-DOX-BSA-NPs. The cetuximab-vc-DOX conjugates adsorbed on the surface of the BSA nanoparticles were determined and optimized by size exclusion chromatography. An in vitro cytotoxicity study was conducted using a colon carcinoma cell line with different EGFR-expression levels to test the selectivity of cetuximab-vc-DOX-NPs.

RESULTS

The vc-DOX and cetuximab-vc-DOX conjugates were both synthesized successfully and their structural characteristics confirmed by H-NMR and SDS-PAGE. The MTT assay showed stronger cytotoxicity of cetuximab-vc-DOX-NPs versus control IgG-vc-DOX-NPs in EGFR-overexpressing RKO cells. Cellular binding and intracellular accumulation determined by flow cytometry and confocal laser scanning microscopy revealed the strong binding ability of cetuximab-vc-DOX-NPs to RKO cells. The in vivo imaging study demonstrated that cetuximab-vc-DOX-NPs exhibited higher fluorescent intensity in tumor tissues than non-decorated nanoparticles (IgG-vc-DOX-NPs). In vivo tumor inhibition and survival tests showed that cetuximab-vc-DOX-NPs revealed higher tumor inhibition efficacy and lower systemic toxicity than control IgG-vc-DOX- NPs.

CONCLUSION

The obtained results emphasize that cetuximab-vc-DOX-NPs, with good tumor-targeting ability and low systemic toxicity, are a promising targeting system for drug delivery.

摘要

背景

为了实现化疗药物对恶性组织的靶向递送，对载体进行特定修饰是提高诊断和治疗效率的关键。在本案例中，牛血清白蛋白（BSA）与西妥昔单抗-缬氨酸-瓜氨酸（vc）-阿霉素（DOX）偶联，以靶向表皮生长因子受体（EGFR），并使药物在 EGFR 过表达的肿瘤细胞中释放。

方法

使用马来酰亚胺基己酰基-缬氨酸-瓜氨酸-p-氨基苯甲酰基-p-硝基苯酚（MC-Val-Cit-PAB-PNP）和 DOX 合成 MC-Val-Cit-PAB-DOX，进一步与西妥昔单抗偶联制备抗体药物偶联物（ADC）。然后，通过去溶剂法将 ADC 吸附到牛血清白蛋白纳米颗粒（NPs）表面，制备牛血清白蛋白-西妥昔单抗-vc-DOX 纳米颗粒（cetuximab-vc-DOX-BSA-NPs）。通过尺寸排阻色谱法确定和优化吸附在牛血清白蛋白纳米颗粒表面的西妥昔单抗-vc-DOX 缀合物。使用具有不同 EGFR 表达水平的结肠癌细胞系进行体外细胞毒性研究，以测试 cetuximab-vc-DOX-NPs 的选择性。

结果

成功合成了 vc-DOX 和 cetuximab-vc-DOX 缀合物，并通过 H-NMR 和 SDS-PAGE 确认了它们的结构特征。MTT 测定表明，在 EGFR 过表达的 RKO 细胞中，cetuximab-vc-DOX-NPs 比对照 IgG-vc-DOX-NPs 具有更强的细胞毒性。通过流式细胞术和共聚焦激光扫描显微镜确定的细胞结合和细胞内积累表明，cetuximab-vc-DOX-NPs 与 RKO 细胞具有很强的结合能力。体内成像研究表明，cetuximab-vc-DOX-NPs 在肿瘤组织中的荧光强度高于未修饰的纳米颗粒（IgG-vc-DOX-NPs）。体内肿瘤抑制和生存试验表明，cetuximab-vc-DOX-NPs 比对照 IgG-vc-DOX-NPs 具有更高的肿瘤抑制疗效和更低的全身毒性。

结论

研究结果强调了 cetuximab-vc-DOX-NPs 具有良好的肿瘤靶向能力和低全身毒性，是一种有前途的药物递送靶向系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/e49e4d85f9c9/IJN-16-2443-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/d5c8cc8d4ec2/IJN-16-2443-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/c68a50f4b960/IJN-16-2443-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/640bfd998b4d/IJN-16-2443-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/f2ad9e0108e3/IJN-16-2443-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/15e489f968a2/IJN-16-2443-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/9c3f88bccdd2/IJN-16-2443-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/6000b4613773/IJN-16-2443-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/b94fc6702cfa/IJN-16-2443-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/e49e4d85f9c9/IJN-16-2443-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/d5c8cc8d4ec2/IJN-16-2443-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/c68a50f4b960/IJN-16-2443-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/640bfd998b4d/IJN-16-2443-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/f2ad9e0108e3/IJN-16-2443-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/15e489f968a2/IJN-16-2443-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/9c3f88bccdd2/IJN-16-2443-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/6000b4613773/IJN-16-2443-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/b94fc6702cfa/IJN-16-2443-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08cf/8009551/e49e4d85f9c9/IJN-16-2443-g0009.jpg

相似文献

1
EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy.表皮生长因子受体靶向西妥昔单抗-缬氨酸-瓜氨酸（vc）-阿霉素免疫偶联物-负载牛血清白蛋白（BSA）纳米颗粒用于结直肠肿瘤治疗。
Int J Nanomedicine. 2021 Mar 26;16:2443-2459. doi: 10.2147/IJN.S289228. eCollection 2021.
2
Engineered bovine serum albumin-based nanoparticles with pH-sensitivity for doxorubicin delivery and controlled release.基于牛血清白蛋白的纳米粒子，具有 pH 敏感性，用于阿霉素的递送和控制释放。
Drug Deliv. 2020 Dec;27(1):1156-1164. doi: 10.1080/10717544.2020.1797243.
3
Enhanced tumor delivery and antitumor response of doxorubicin-loaded albumin nanoparticles formulated based on a Schiff base.基于席夫碱构建的载多柔比星白蛋白纳米粒的增强肿瘤递药与抗肿瘤效应
Int J Nanomedicine. 2016 Aug 12;11:3875-90. doi: 10.2147/IJN.S108689. eCollection 2016.
4
Folate-receptor mediated pH/reduction-responsive biomimetic nanoparticles for dually activated multi-stage anticancer drug delivery.叶酸受体介导的 pH/还原响应仿生纳米颗粒用于双重激活多阶段抗癌药物递送。
Int J Pharm. 2020 Jul 30;585:119456. doi: 10.1016/j.ijpharm.2020.119456. Epub 2020 May 31.
5
pH-sensitive Au-BSA-DOX-FA nanocomposites for combined CT imaging and targeted drug delivery.用于联合CT成像和靶向药物递送的pH敏感型金-牛血清白蛋白-阿霉素-叶酸纳米复合材料
Int J Nanomedicine. 2017 Apr 6;12:2829-2843. doi: 10.2147/IJN.S128270. eCollection 2017.
6
In vitro evaluation of doxorubicin-incorporated magnetic albumin nanospheres.阿霉素负载磁性白蛋白纳米球的体外评价
Chem Biol Drug Des. 2014 Jul;84(1):108-15. doi: 10.1111/cbdd.12300. Epub 2014 May 12.
7
Liver cancer targeting of Doxorubicin with reduced distribution to the heart using hematoporphyrin-modified albumin nanoparticles in rats.载血卟啉白蛋白纳米粒用于大鼠肝癌靶向给药、减少心脏分布的阿霉素研究
Pharm Res. 2012 Mar;29(3):795-805. doi: 10.1007/s11095-011-0603-6. Epub 2011 Oct 5.
8
In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts.西妥昔单抗偶联聚（γ-谷氨酸）-多西他赛纳米药物在表皮生长因子受体过表达的胃癌异种移植瘤中的体内评价
Int J Nanomedicine. 2017 Sep 30;12:7165-7182. doi: 10.2147/IJN.S143529. eCollection 2017.
9
Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for overcoming multidrug-resistant in cancer cells.载有阿霉素的甜甜圈形状牛血清白蛋白纳米粒用于克服癌细胞的多药耐药性。
Int J Biol Macromol. 2018 Feb;107(Pt B):1835-1843. doi: 10.1016/j.ijbiomac.2017.10.041. Epub 2017 Oct 10.
10
Preparation of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles for hepatocellular carcinoma-targeted drug delivery.载 10-羟基喜树碱的甘草酸偶联牛血清白蛋白纳米粒的制备及其用于肝癌靶向给药。
Int J Nanomedicine. 2013;8:1207-22. doi: 10.2147/IJN.S40493. Epub 2013 Mar 27.

引用本文的文献

1
The Co-Delivery of Natural Products and Small RNAs for Cancer Therapy: A Review.用于癌症治疗的天然产物与小RNA的联合递送：综述
Molecules. 2025 Mar 27;30(7):1495. doi: 10.3390/molecules30071495.
2
Surface Functionalization of Nanocarriers with Anti-EGFR Ligands for Cancer Active Targeting.用于癌症主动靶向的抗表皮生长因子受体（EGFR）配体修饰纳米载体的表面功能化
Nanomaterials (Basel). 2025 Jan 21;15(3):158. doi: 10.3390/nano15030158.
3
Enhanced drug delivery with nanocarriers: a comprehensive review of recent advances in breast cancer detection and treatment.

本文引用的文献

1
Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for overcoming multidrug-resistant in cancer cells.载有阿霉素的甜甜圈形状牛血清白蛋白纳米粒用于克服癌细胞的多药耐药性。
Int J Biol Macromol. 2018 Feb;107(Pt B):1835-1843. doi: 10.1016/j.ijbiomac.2017.10.041. Epub 2017 Oct 10.
2
Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia.伪装在血小板膜涂层中的纳米颗粒作为抗体诱饵用于治疗免疫性血小板减少症。
Biomaterials. 2016 Dec;111:116-123. doi: 10.1016/j.biomaterials.2016.10.003. Epub 2016 Oct 5.
3
Dual-functional bio-derived nanoparticulates for apoptotic antitumor therapy.
纳米载体增强药物递送：乳腺癌检测与治疗最新进展综述
Discov Nano. 2024 Sep 7;19(1):143. doi: 10.1186/s11671-024-04086-6.
4
Biological role and expression of translationally controlled tumor protein (TCTP) in tumorigenesis and development and its potential for targeted tumor therapy.翻译控制肿瘤蛋白（TCTP）在肿瘤发生发展中的生物学作用、表达及其在肿瘤靶向治疗中的潜力。
Cancer Cell Int. 2024 Jun 4;24(1):198. doi: 10.1186/s12935-024-03355-9.
5
Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior.载仑伐替尼聚乳酸-羟基乙酸纳米粒偶联表皮生长因子受体抗体作为一种临床前方法治疗具有侵袭性行为的甲状腺癌。
Biomolecules. 2023 Nov 13;13(11):1647. doi: 10.3390/biom13111647.
6
Use of Albumin for Drug Delivery as a Diagnostic and Therapeutic Tool.白蛋白作为药物递送载体用于诊断和治疗的研究进展。
Curr Pharm Biotechnol. 2024;25(6):676-693. doi: 10.2174/1389201024666230807161200.
7
Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment.响应组织蛋白酶B活性的癌症治疗智能递送系统
Pharmaceutics. 2023 Jun 29;15(7):1848. doi: 10.3390/pharmaceutics15071848.
8
Antibody-Functionalized Nanoformulations for Targeted Therapy of Colorectal Cancer: A Systematic Review.抗体功能化纳米制剂用于结直肠癌的靶向治疗：系统评价。
Int J Nanomedicine. 2022 Oct 31;17:5065-5080. doi: 10.2147/IJN.S368814. eCollection 2022.
9
EGFR-Based Targeted Therapy for Colorectal Cancer-Promises and Challenges.基于表皮生长因子受体的结直肠癌靶向治疗：前景与挑战
Vaccines (Basel). 2022 Mar 24;10(4):499. doi: 10.3390/vaccines10040499.
10
Chlorambucil-Iron Oxide Nanoparticles as a Drug Delivery System for Leukemia Cancer Cells.氯苯丁酸-氧化铁纳米颗粒作为白血病癌细胞的药物传递系统。
Int J Nanomedicine. 2021 Sep 8;16:6205-6216. doi: 10.2147/IJN.S312752. eCollection 2021.
双功能生物衍生纳米颗粒用于细胞凋亡抗肿瘤治疗。
Biomaterials. 2015 Dec;72:90-103. doi: 10.1016/j.biomaterials.2015.08.051. Epub 2015 Aug 31.
4
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression.SPINK1通过下调金属硫蛋白的表达促进结直肠癌进展。
Oncogenesis. 2015 Aug 10;4(8):e162. doi: 10.1038/oncsis.2015.23.
5
Expression of pEGFR and pAKT as response-predictive biomarkers for RAS wild-type patients to anti-EGFR monoclonal antibodies in metastatic colorectal cancers.pEGFR和pAKT作为RAS野生型转移性结直肠癌患者对抗表皮生长因子受体单克隆抗体反应预测生物标志物的表达
Br J Cancer. 2015 Aug 11;113(4):680-5. doi: 10.1038/bjc.2015.250. Epub 2015 Jul 14.
6
Systematic study on the preparation of BSA nanoparticles.牛血清白蛋白纳米颗粒制备的系统研究。
Colloids Surf B Biointerfaces. 2014 Nov 1;123:286-92. doi: 10.1016/j.colsurfb.2014.09.028. Epub 2014 Sep 22.
7
Recent In Vivo Evidences of Particle-Based Delivery of Small-Interfering RNA (siRNA) into Solid Tumors.基于颗粒的小干扰RNA（siRNA）向实体瘤体内递送的最新证据
J Pharm Innov. 2014 Jun 1;9(2):158-173. doi: 10.1007/s12247-014-9183-4.
8
Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis.通过重建的高密度脂蛋白直接胞质内递送 siRNA 用于肿瘤血管生成的靶向治疗。
Biomaterials. 2014 Aug;35(25):7214-27. doi: 10.1016/j.biomaterials.2014.05.009. Epub 2014 May 27.
9
Novel designed polyoxyethylene nonionic surfactant with improved safety and efficiency for anticancer drug delivery.新型设计的聚氧乙烯非离子表面活性剂，用于抗癌药物递送时安全性和效率更高。
Int J Nanomedicine. 2014 Apr 28;9:2089-100. doi: 10.2147/IJN.S60667. eCollection 2014.
10
Interaction between cell-penetrating peptides and acid-sensitive anionic oligopeptides as a model for the design of targeted drug carriers.细胞穿透肽与酸敏性阴离子寡肽之间的相互作用作为靶向药物载体设计的模型。
Mol Pharm. 2014 May 5;11(5):1583-90. doi: 10.1021/mp400747k. Epub 2014 Apr 15.