Cetuximab scFv-Modified 5-FU Loaded Chitosan Nanoparticles: "A Novel Therapeutic Platform."

IF 2.2 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current pharmaceutical biotechnology Pub Date : 2024-10-31 DOI:10.2174/0113892010340791241025033549

Masumeh Jalalvand, Fariba Esmaeili, Khadijeh Falahzadeh, Mohammadali Mazloumi, Gholamreza Shahsavari, Elham Bayat, Farshid Zandsalimi, Yeganeh Talebkhan, Leila Nematollahi, Babak Negahdari

{"title":"Cetuximab scFv-Modified 5-FU Loaded Chitosan Nanoparticles: \"A Novel Therapeutic Platform.\"","authors":"Masumeh Jalalvand, Fariba Esmaeili, Khadijeh Falahzadeh, Mohammadali Mazloumi, Gholamreza Shahsavari, Elham Bayat, Farshid Zandsalimi, Yeganeh Talebkhan, Leila Nematollahi, Babak Negahdari","doi":"10.2174/0113892010340791241025033549","DOIUrl":null,"url":null,"abstract":"Background: Colorectal cancer [CRC] is among the most fatal types of cancer. An active targeting delivery system that specifically interacts with CRC cells could improve the therapy's outcomes. Herein, Cetuximab single-chain fragment variable antibody [scFv] fragments were conjugated to the surface of 5-FU encapsulated chitosan nanoparticles [CS NPs] to develop an effective therapeutic platform [scFv-CS/5-FU NPs].Method: CS/5-FU NPs were synthesized using a special fluidic system. Encapsulation efficiency [EE], loading capacity [LC], and the drug release profile of the particles were determined. scFv fragments were produced recombinantly and tailored on the surface of CS/5-FU NPs. The physicochemical features of scFv-CS/5-FU NPs were also characterized. MTT and flow cytometry assay investigated the toxicity effect of scFv-CS/5-FU NPs on the HCT116 cell line.Results: CS/5-FU NPs had a homogenous spherical shape. They possessed sustainable drugrelease behavior. The produced scFv-CS/5-FU NPs were also spherical. scFv-CS/5-FU NPs significantly decreased the viability of cancerous cells in a dose-dependent manner and induced apoptosis in 97.97% of targeted cells.Conclusion: scFv-CS/5-FU NPs showed remarkable anti-CRC activity. This novel targeting delivery system reduced the effective dose of 5-FU which is of vital importance to decrease the devastating side effects of chemotherapy.","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current pharmaceutical biotechnology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113892010340791241025033549","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Colorectal cancer [CRC] is among the most fatal types of cancer. An active targeting delivery system that specifically interacts with CRC cells could improve the therapy's outcomes. Herein, Cetuximab single-chain fragment variable antibody [scFv] fragments were conjugated to the surface of 5-FU encapsulated chitosan nanoparticles [CS NPs] to develop an effective therapeutic platform [scFv-CS/5-FU NPs].

Method: CS/5-FU NPs were synthesized using a special fluidic system. Encapsulation efficiency [EE], loading capacity [LC], and the drug release profile of the particles were determined. scFv fragments were produced recombinantly and tailored on the surface of CS/5-FU NPs. The physicochemical features of scFv-CS/5-FU NPs were also characterized. MTT and flow cytometry assay investigated the toxicity effect of scFv-CS/5-FU NPs on the HCT116 cell line.

Results: CS/5-FU NPs had a homogenous spherical shape. They possessed sustainable drugrelease behavior. The produced scFv-CS/5-FU NPs were also spherical. scFv-CS/5-FU NPs significantly decreased the viability of cancerous cells in a dose-dependent manner and induced apoptosis in 97.97% of targeted cells.

Conclusion: scFv-CS/5-FU NPs showed remarkable anti-CRC activity. This novel targeting delivery system reduced the effective dose of 5-FU which is of vital importance to decrease the devastating side effects of chemotherapy.

查看原文本刊更多论文

西妥昔单抗 scFv 修饰的 5-FU 负载壳聚糖纳米颗粒："新型治疗平台"。

背景：结直肠癌是最致命的癌症之一。一种能与 CRC 细胞发生特异性相互作用的主动靶向递送系统可提高治疗效果。本文将西妥昔单抗单链片段可变抗体[scFv]片段与 5-FU 包封壳聚糖纳米颗粒[CS NPs]表面共轭，以开发一种有效的治疗平台[scFv-CS/5-FU NPs]：方法：采用特殊流体系统合成CS/5-FU NPs。方法：采用特殊的流化体系合成了 CS/5-FU NPs，测定了颗粒的包封效率[EE]、载药量[LC]和药物释放曲线。此外，还对 scFv-CS/5-FU NPs 的理化特性进行了表征。MTT和流式细胞术检测了scFv-CS/5-FU NPs对HCT116细胞株的毒性效应：结果：CS/5-FU NPs呈均匀的球形。结果：CS/5-FU NPs 具有均匀的球形，并具有可持续的药物释放行为。产生的 scFv-CS/5-FU NPs 也是球形的。scFv-CS/5-FU NPs 以剂量依赖的方式显著降低了癌细胞的存活率，并诱导了 97.97% 的靶向细胞凋亡。结论：scFv-CS/5-FU NPs 具有显著的抗癌活性，这种新型靶向递送系统降低了 5-FU 的有效剂量，对减少化疗的破坏性副作用至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Current pharmaceutical biotechnology 医学-生化与分子生物学

CiteScore

5.60

自引率

3.60%

发文量

203

审稿时长

6 months

期刊介绍： Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.