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用于靶向激活天然免疫细胞的荧光纳米金刚石的抗体偶联

Antibody Conjugation of Fluorescent Nanodiamonds for Targeted Innate Immune Cell Activation.

作者信息

Suarez-Kelly Lorena P, Sun Steven H, Ren Casey, Rampersaud Isaac V, Albertson David, Duggan Megan C, Noel Tiffany C, Courtney Nicholas, Buteyn Nathaniel J, Moritz Charles, Yu Lianbo, Yildiz Vedat O, Butchar Jonathan P, Tridandapani Susheela, Rampersaud Arfaan A, Carson William E

机构信息

The Arthur G. James Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.

Department of Surgery, The Ohio State University, Columbus, Ohio 43210, United States.

出版信息

ACS Appl Nano Mater. 2021 Mar 26;4(3):3122-3139. doi: 10.1021/acsanm.1c00256. Epub 2021 Mar 11.

Abstract

BACKGROUND

fluorescent nanodiamonds (FND) are nontoxic, infinitely photostable nanoparticles that emit near-infrared fluorescence and have a modifiable surface allowing for the generation of protein-FND conjugates. FND-mediated immune cell targeting may serve as a strategy to visualize immune cells and promote immune cell activation.

METHODS

uncoated-FND (uFND) were fabricated, coated with glycidol (gFND), and conjugated with immunoglobulin G (IgG-gFND). studies were performed using a breast cancer/natural killer/monocyte co-culture system, and studies were performed using a breast cancer mouse model.

RESULTS

studies demonstrated the targeted immune cell uptake of IgG-gFND, resulting in significant immune cell activation and no compromise in immune cell viability. IgG-gFND remained at the tumor site following intratumoral injection compared to uFND which migrated to the liver and kidneys.

CONCLUSION

antibody-conjugated FND may serve as immune drug delivery vehicles with "track and trace capabilities" to promote directed antitumor activity and minimize systemic toxicities.

摘要

背景

荧光纳米金刚石(FND)是无毒、具有无限光稳定性的纳米颗粒,可发射近红外荧光,其表面可修饰,能够生成蛋白质-FND缀合物。FND介导的免疫细胞靶向可作为一种可视化免疫细胞并促进免疫细胞激活的策略。

方法

制备未包被的FND(uFND),用缩水甘油包被(gFND),并与免疫球蛋白G缀合(IgG-gFND)。使用乳腺癌/自然杀伤细胞/单核细胞共培养系统进行研究,并使用乳腺癌小鼠模型进行研究。

结果

研究证明了IgG-gFND对免疫细胞的靶向摄取,导致显著的免疫细胞激活且不影响免疫细胞活力。与迁移至肝脏和肾脏的uFND相比,瘤内注射后IgG-gFND保留在肿瘤部位。

结论

抗体缀合的FND可作为具有“追踪能力”的免疫药物递送载体,以促进定向抗肿瘤活性并将全身毒性降至最低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c155/8202965/33d6c09c03b3/an1c00256_0002.jpg

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