使用西妥昔单抗结合淀粉靶向siRNA递送表皮生长因子受体驱动的头颈部鳞状细胞癌。

IF 8.3 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Small Science Pub Date : 2025-05-15 eCollection Date: 2025-07-01 DOI:10.1002/smsc.202500073
Chen Benafsha, Limor Cohen, Leah Shimonov, Riki Goldbart, Tamar Traitel, Eliz Amar-Lewis, Ramesh Chintakunta, Manu Parasad, Uzi Hadad, Moshe Elkabets, Joseph Kost
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引用次数: 0

摘要

小干扰RNA (siRNA)疗法具有通过靶向特定信使RNA (mRNA)序列破坏致癌信号通路的巨大潜力。然而,其临床应用受到开发有效给药系统的挑战的限制。本研究利用淀粉这种具有生物相容性和可生物降解的天然多糖作为载体,提高siRNA的稳定性和传递效率。通过将西妥昔单抗与siRNA的季铵化淀粉(q -淀粉)偶联,对过度表达表皮生长因子受体(EGFR)的癌细胞实现了更高的特异性。本研究包括这些靶向复合物的合成、表征和生物学评价,这些靶向复合物在体外证明了有效的细胞摄取和靶向敲除。此外,这些复合物表现出显著的肿瘤特异性积累,显著增强了egfr过表达肿瘤在体内的活性靶向性。这些发现强调了复合物在表达egfr的头颈部鳞状细胞癌中积累的潜力,促进了淀粉基递送系统的发展,并为进一步的诊断和治疗应用铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeted siRNA Delivery Using Cetuximab-Conjugated Starch for Epidermal Growth Factor Receptor-Driven Head and Neck Squamous Cell Carcinoma.

Targeted siRNA Delivery Using Cetuximab-Conjugated Starch for Epidermal Growth Factor Receptor-Driven Head and Neck Squamous Cell Carcinoma.

Targeted siRNA Delivery Using Cetuximab-Conjugated Starch for Epidermal Growth Factor Receptor-Driven Head and Neck Squamous Cell Carcinoma.

Targeted siRNA Delivery Using Cetuximab-Conjugated Starch for Epidermal Growth Factor Receptor-Driven Head and Neck Squamous Cell Carcinoma.

Small interfering RNA (siRNA) therapy holds significant potential to disrupt oncogenic signaling pathways by targeting specific messenger RNA (mRNA) sequences. However, its clinical application is limited by challenges in developing effective delivery systems. In this study, starch, a biocompatible and biodegradable natural polysaccharide, is utilized as a carrier to enhance siRNA stability and delivery efficiency. By conjugating cetuximab to quaternized starch (Q-starch) complexed with the siRNA, an increased specificity is achieved toward cancer cells overexpressing the epidermal growth factor receptor (EGFR). This research encompasses the synthesis, characterization, and biological evaluation of these targeted complexes, which demonstrate efficient cellular uptake and on-target knockdown in vitro. Furthermore, these complexes exhibit notable tumor-specific accumulation, significantly enhancing the active targeting of EGFR-overexpressing tumors in vivo. These findings highlight the potential of the complexes to accumulate in EGFR-expressing head and neck squamous cell carcinoma, advancing the development of starch-based delivery systems and paving the way for further diagnostic and therapeutic applications.

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来源期刊
CiteScore
14.00
自引率
2.40%
发文量
0
期刊介绍: Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.
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