Zn-Dipicolylamine-Based ROS-Responsive Bola-Lipid Nanoparticles for Efficient Protein Delivery and Tumor Immunotherapy,ACS Applied Nano Materials

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Zn-Dipicolylamine-Based ROS-Responsive Bola-Lipid Nanoparticles for Efficient Protein Delivery and Tumor Immunotherapy
ACS Applied Nano Materials ( IF 5.3 ) Pub Date : 2023-11-20 , DOI: 10.1021/acsanm.3c04192
Rui-Mo Zhao ₁ , Yue Hu ₁ , Ping Chen ₁ , Meng-Wei Hei ₁ , Xiao-Qi Yu ₁ , Ji Zhang ₁

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In recent years, remarkable progress has been made in cancer immunotherapy. Lipid nanoparticles (LNPs) may serve as an ideal platform for antigen delivery since the lipid structure may be rationally designed and altered to provide the LNPs with specific properties. In this study, a series of ROS-sensitive cationic bola-lipids n-TDZn, in which Zn-DPA was introduced as a hydrophilic headgroup to enhance protein binding, were designed and synthesized. The length of hydrophobic linkage might have effect on the physical properties of the formed LNPs such as particle size and surface potential. The nanosized lipoplex formed from 14-TDZn with the smallest particle size and highest positive potential could induce higher cellular uptake. β-Galactosidase (β-Gal) assay showed that the lipoplexes could efficiently deliver protein into the cells without the loss of protein activity. Subsequent antigen delivery by the lipoplexes demonstrated that the 14-TDZn/OVA lipoplex could well mediate cell internalization and promote the maturation and antigen presentation of bone marrow-derived dendritic cells (BMDCs). Further, in vivo antitumor assays exhibited that 14-TDZn/OVA lipoplex could effectively inhibit tumor growth and enhance T-cell infiltration in tumor tissues, suggesting the activation of the immune system. These results provide a candidate for efficient antigen protein delivery and tumor vaccines.

中文翻译：

基于 Zn-二吡啶胺的 ROS 响应性 Bola-Lipid 纳米颗粒，用于高效蛋白质递送和肿瘤免疫治疗

近年来，癌症免疫治疗取得了显着进展。脂质纳米颗粒（LNP）可以作为抗原递送的理想平台，因为可以合理地设计和改变脂质结构以提供具有特定性质的LNP。在本研究中，设计并合成了一系列ROS敏感的阳离子波拉脂质n -TDZn，其中引入Zn-DPA作为亲水头基以增强蛋白质结合。疏水键的长度可能会影响所形成的 LNP 的物理性质，例如粒径和表面电位。由14-TDZn形成的纳米脂质复合物具有最小的粒径和最高的正电势，可以诱导更高的细胞摄取。β-半乳糖苷酶（β-Gal）测定表明，脂质复合物可以有效地将蛋白质递送到细胞中，而不会损失蛋白质活性。随后的脂质复合物递送抗原表明，14-TDZn /OVA 脂质复合物可以很好地介导细胞内化并促进骨髓源性树突状细胞（BMDC）的成熟和抗原呈递。此外，体内抗肿瘤试验表明，14-TDZn /OVA lipoplex可以有效抑制肿瘤生长并增强肿瘤组织中的T细胞浸润，表明免疫系统的激活。这些结果为有效的抗原蛋白递送和肿瘤疫苗提供了候选。

更新日期：2023-11-20

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