Antiangiogenic Antheraea pernyi Silk Fibroin Nanocarrier As an Advanced Dual-Gene Delivery Platform for Lung Tumor Suppression.

IF 5.4 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-10-09 DOI:10.1021/acs.biomac.5c01484

Jing Qu, Xueping Liu, Jiru Jia, Wei Ma, Qi Xiao, Mingzhong Li

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引用次数: 0

Abstract

The cationic Antheraea pernyi silk fibroin (CASF)-bridged endostatin peptide 2 (ES2) electrostatically coated the inhibitor of growth 4 (ING4)/interleukin-24 (IL-24) dual-gene coexpression plasmid DNA (pDNA) to construct a CASF-ES2/pDNA nanocarrier, which significantly enhanced gene expression and induced apoptosis by strengthening cell adhesion and endocytosis. The continuously released ES2 contributed to its specific action on HUVECs, including inducing apoptosis and hindering migration, invasion, and tube formation, as well as inhibiting angiogenesis in the chorioallantoic membrane. In the treatment of mice with A549 xenograft tumors, CASF-ES2/pDNA arrested the growth cycle of tumor cells and activated the Bcl-2/Bax/C Caspase-3 apoptotic pathway, promoting cell apoptosis and tissue collapse. Additionally, the released ES2 prevented the formation of tumor neovasculature, cut off the nutrient channels for tumor growth, and synergistically inhibited the development and metastasis of xenograft tumors. This safe and antiangiogenic gene vector shows great promise for application in long-term antitumor and antimetastatic therapy.

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抗血管生成柞蚕丝素纳米载体作为肺肿瘤抑制的先进双基因传递平台。

将阳离子柞蚕丝素蛋白(CASF)-桥接内皮抑素肽2 (ES2) -静电包被生长抑制因子4 (ING4)/白介素-24 （IL-24）双基因共表达质粒DNA (pDNA)，构建CASF-ES2/pDNA纳米载体，通过增强细胞黏附和内吞作用，显著提高基因表达，诱导细胞凋亡。持续释放的ES2有助于其对HUVECs的特异性作用，包括诱导凋亡，阻碍迁移、侵袭和成管，以及抑制绒毛膜尿囊膜的血管生成。在A549异种移植肿瘤小鼠的治疗中，CASF-ES2/pDNA阻滞肿瘤细胞的生长周期，激活Bcl-2/Bax/C Caspase-3凋亡通路，促进细胞凋亡和组织塌陷。此外，释放的ES2阻止肿瘤新生血管的形成，切断肿瘤生长的营养通道，协同抑制异种移植肿瘤的发展和转移。这种安全的抗血管生成基因载体在长期抗肿瘤和抗转移治疗中具有广阔的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.