Cholesterol modified defense peptide as an EMP2-siRNA delivery system for synergistic immunogene therapy against breast cancer

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio Pub Date : 2025-09-18 DOI:10.1016/j.mtbio.2025.102321

Xiaoyun Wang , Siliang Chen , Gu He , Yanghui Zhu , Nan Zhang , Changyang Gong , Xiang Li , Yujuan Chen

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Abstract

Epithelial membrane protein 2 (EMP2) plays crucial roles in cell proliferation, migration, and adhesion. Despite its importance, conventional EMP2 RNAi therapy shows limited efficacy in vivo. We therefore developed a novel RNA-delivery system utilizing self-assembling defense peptide-cholesterol conjugates for efficient EMP2-siRNA transfection. The engineered HH2-siEMP2 nanoparticles exhibited optimal size and positive surface charge, conferring excellent serum stability and enhanced cellular uptake in breast cancer cell lines. These nanoparticles effectively silenced EMP2 expression, leading to significant suppression of tumor migration and invasion in both in vitro and in vivo models. Beyond direct anti-tumor effects, the HH2-C conjugate demonstrated immunomodulatory properties by promoting Th1 cell expansion, reducing Th2 cells and immunosuppressive Tregs, and restoring Th17/Treg balance. These findings establish EMP2 as a promising therapeutic target in breast cancer and highlight the potential of HH2-C-based nanoparticles as a dual-function platform combining efficient siRNA delivery with immunostimulatory activity.

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胆固醇修饰防御肽作为EMP2-siRNA递送系统用于协同免疫基因治疗乳腺癌

上皮膜蛋白2 （Epithelial membrane protein 2, EMP2）在细胞增殖、迁移和粘附中起着至关重要的作用。尽管其重要性，传统的EMP2 RNAi疗法在体内的疗效有限。因此，我们开发了一种新的rna递送系统，利用自组装防御肽-胆固醇偶联物高效转染EMP2-siRNA。设计的HH2-siEMP2纳米颗粒具有最佳的尺寸和正表面电荷，具有良好的血清稳定性和增强乳腺癌细胞系的细胞摄取。这些纳米颗粒有效地沉默了EMP2的表达，从而在体外和体内模型中显著抑制了肿瘤的迁移和侵袭。除了直接的抗肿瘤作用外，HH2-C缀合物还通过促进Th1细胞扩增，减少Th2细胞和免疫抑制Treg，恢复Th17/Treg平衡，显示出免疫调节特性。这些发现表明EMP2是一个很有前景的乳腺癌治疗靶点，并强调了基于hh2 - c的纳米颗粒作为一种结合高效siRNA传递和免疫刺激活性的双重功能平台的潜力。

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来源期刊

Materials Today Bio Multiple-

CiteScore

8.30

自引率

4.90%

发文量

303

审稿时长

30 days

期刊介绍： Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).