抗体功能化靶向儿科神经母细胞瘤的新型表观遗传纳米疗法。

IF 5.6 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces Pub Date : 2025-09-10 DOI:10.1016/j.colsurfb.2025.115137

Avinash Chandra Kushwaha, Mohd Ayoub, Devraj Sarkar, Surajit Karmakar, Subhasree Roy Choudhury

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引用次数: 0

摘要

神经母细胞瘤是一种异质性、恶性、颅外的儿童期神经嵴交感肾上腺系肿瘤，主要累及肾上腺。多梳蛋白Bmi1在神经母细胞瘤的发生过程中高度表达，并通过其E3连接酶活性对几种下游标记物进行表观遗传调控。特异性抑制剂PRT4165抑制Bmi1具有治疗潜力，但脱靶等局限性阻碍了其应用。为了实现bmi1特异性靶向纳米治疗，prt4165包被和抗gd2修饰（用于主动靶向神经母细胞瘤）的人血清白蛋白纳米颗粒（PRT@HSANPs@GD2）被引入神经母细胞瘤治疗。PRT@HSANPs@GD2通过GD2+神经母细胞瘤细胞凋亡增强细胞内化和细胞毒性。此外，PRT@HSANPs@GD2表现出较好的肿瘤体积回归和Bmi1的下调。此外，我们首次报道了Bmi1和Oct3/4以及Oct3/4和Vimentin在神经母细胞瘤中的相互作用，其中我们的纳米制剂PRT@HSANPs@GD2抑制了Bmi1和Oct3/4以及Oct3/4和Vimentin在神经母细胞瘤中的相互作用。通过包裹PRT4165的纳米颗粒靶向GD2是一种创新的神经母细胞瘤靶向纳米治疗方案，具有未来转化开发的潜力。

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Antibody functionalized targeted novel epigenetic nanotherapy for paediatric neuroblastoma

The neuroblastoma is the most heterogeneous, malignant, extracranial, childhood cancer of the embryonic sympathoadrenal lineage of the neural crest which mainly affect the adrenal glands. The polycomb protein, Bmi1, is highly expressed in the neuroblastoma tumorigenesis and executes epigenetic regulation of several downstream markers through its E3 ligase activity. The suppression of Bmi1 with a specific inhibitor, PRT4165, possesses a therapeutic potential but limitations such as off targeting impede its applications. In order to manifest Bmi1-specific targeted nanotherapy, PRT4165-encapsulated and anti-GD2-decorated (for active targeting of neuroblastoma) human serum albumin nanoparticles (PRT@HSANPs@GD2) are introduced as neuroblastoma therapy. PRT@HSANPs@GD2 enhance the cellular internalization and cytotoxicity through apoptosis in the GD2⁺ neuroblastoma cells. Furthermore, PRT@HSANPs@GD2 exhibit superior regression of tumor volumes, and downregulation of Bmi1. In addition, we report Bmi1 and Oct3/4 along with Oct3/4 and Vimentin interactions in neuroblastoma for the first-time wherein our nanoformulation, PRT@HSANPs@GD2, repress the Bmi1 and Oct3/4 along with Oct3/4 and Vimentin interactions in neuroblastoma. The GD2 targeting through nanoparticles-encapsulated with PRT4165 is an innovative and novel targeted nanotherapy regimen for the neuroblastoma with a future potential of translational development.

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来源期刊

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.