Apatinib-loaded silicate nanoparticles coated with macrophage membranes and PD-1 antibody for enhanced chemo-immunotherapy in ovarian cancer via VEGFR2 and PD-1 dual inhibition

IF 5.4 2区 医学 Q1 BIOPHYSICS
Hongru Li , Yuhan Wang , Shunqing Zhou , Jianli Liu , Yuemei Jin
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Abstract

Ovarian cancer remains one of the most challenging malignancies to treat due to its aggressive nature and resistance to conventional therapies. In this study, we developed a nanoparticle-based system (Apa@SiO2@MP) that combines chemotherapy with immune checkpoint inhibition for enhanced treatment of ovarian cancer. The system consists of mesoporous silica nanoparticles (SiO2 NPs) coated with macrophage membranes (MP) and functionalized with programmed death 1 (PD-1) antibody, designed to improve the delivery and targeting of apatinib, a tyrosine kinase inhibitor. The system demonstrated effective drug encapsulation, controlled release, and stability in physiological environments. In vitro assays revealed that Apa@SiO2@MP had minimal cytotoxicity in normal cells but significantly reduced cell viability in ovarian cancer cells (SKOV-3), highlighting its cancer-targeting ability. Apatinib effectively inhibited VEGFR2 expression and induced reactive oxygen species (ROS) production, further promoting anti-cancer effects. In vivo, Apa@SiO2@MP treatment led to enhanced tumor inhibition, as well as significant immune response activation, including increased CD4+ and CD8+ T cells and elevated IFN-γ levels. This study provides a promising multi-modal strategy for overcoming challenges in cancer therapy by integrating chemotherapy, immunotherapy, and targeted drug delivery, offering potential for improved treatment outcomes in ovarian cancer.
负载apatinib的硅酸盐纳米颗粒包被巨噬细胞膜和PD-1抗体,通过VEGFR2和PD-1双重抑制增强卵巢癌的化学免疫治疗
由于卵巢癌的侵袭性和对传统疗法的耐药性,它仍然是最具挑战性的恶性肿瘤之一。在这项研究中,我们开发了一种基于纳米颗粒的系统(Apa@SiO2@MP),将化疗与免疫检查点抑制相结合,以增强卵巢癌的治疗。该系统由巨噬细胞膜(MP)包裹的介孔二氧化硅纳米颗粒(SiO2 NPs)和程序性死亡1 (PD-1)抗体组成,旨在改善阿帕替尼(酪氨酸激酶抑制剂)的递送和靶向性。该系统具有良好的药物包封性、控释性和生理环境稳定性。体外实验显示Apa@SiO2@MP在正常细胞中具有最小的细胞毒性,但在卵巢癌细胞(SKOV-3)中显著降低细胞活力,突出了其靶向癌症的能力。阿帕替尼有效抑制VEGFR2表达,诱导活性氧(ROS)产生,进一步促进抗癌作用。在体内,Apa@SiO2@MP治疗导致肿瘤抑制增强,以及显著的免疫反应激活,包括CD4+和CD8+ T细胞增加和IFN-γ水平升高。本研究提供了一种有希望的多模式策略,通过结合化疗、免疫治疗和靶向给药来克服癌症治疗中的挑战,为改善卵巢癌的治疗结果提供了潜力。
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来源期刊
Colloids and Surfaces B: Biointerfaces
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.
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