当前位置: X-MOL 学术Nat. Nanotechnol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Polymersomes with splenic avidity target red pulp myeloid cells for cancer immunotherapy
Nature Nanotechnology ( IF 38.1 ) Pub Date : 2024-07-31 , DOI: 10.1038/s41565-024-01727-w
Annelies C Wauters 1 , Jari F Scheerstra 1 , Mandy M T van Leent 2, 3 , Abraham J P Teunissen 2, 3, 4 , Bram Priem 2, 5, 6 , Thijs J Beldman 7 , Nils Rother 8 , Raphaël Duivenvoorden 2, 8 , Geoffrey Prévot 2 , Jazz Munitz 2 , Yohana C Toner 7 , Jeroen Deckers 7 , Yuri van Elsas 7 , Patricia Mora-Raimundo 9 , Gal Chen 9 , Sheqouia A Nauta 2 , Anna Vera D Verschuur 2 , Arjan W Griffioen 6 , David P Schrijver 10 , Tom Anbergen 7 , Yudong Li 1 , Hanglong Wu 1 , Alexander F Mason 1 , Marleen H M E van Stevendaal 1 , Ewelina Kluza 10 , Richard A J Post 11 , Leo A B Joosten 7, 12 , Mihai G Netea 7, 13 , Claudia Calcagno 2 , Zahi A Fayad 2 , Roy van der Meel 10 , Avi Schroeder 9 , Loai K E A Abdelmohsen 1 , Willem J M Mulder 7, 10 , Jan C M van Hest 1
Affiliation  

Regulating innate immunity is an emerging approach to improve cancer immunotherapy. Such regulation requires engaging myeloid cells by delivering immunomodulatory compounds to hematopoietic organs, including the spleen. Here we present a polymersome-based nanocarrier with splenic avidity and propensity for red pulp myeloid cell uptake. We characterized the in vivo behaviour of four chemically identical yet topologically different polymersomes by in vivo positron emission tomography imaging and innovative flow and mass cytometry techniques. Upon intravenous administration, relatively large and spherical polymersomes accumulated rapidly in the spleen and efficiently targeted myeloid cells in the splenic red pulp. When loaded with β-glucan, intravenously administered polymersomes significantly reduced tumour growth in a mouse melanoma model. We initiated our nanotherapeutic’s clinical translation with a biodistribution study in non-human primates, which revealed that the platform’s splenic avidity is preserved across species.



中文翻译:


具有脾亲和力的聚合物体靶向红髓髓细胞,用于癌症免疫治疗



调节先天免疫是改进癌症免疫疗法的一种新兴方法。这种调节需要通过将免疫调节化合物递送到造血器官(包括脾脏)来参与骨髓细胞。在这里,我们提出了一种基于聚合物体的纳米载体,具有脾亲和力和红髓髓细胞摄取倾向。我们通过体内正电子发射断层扫描成像以及创新的流式和质谱流式细胞术技术表征了四种化学相同但拓扑不同的聚合物体的体内行为。静脉给药后,相对较大的球形聚合物体在脾脏中迅速积累,并有效地靶向脾红髓中的髓细胞。当加载 β-葡聚糖时,静脉内给药的聚合物体显着减少了小鼠黑色素瘤模型中的肿瘤生长。我们通过在非人灵长类动物中进行生物分布研究来启动纳米疗法的临床转化,该研究发现该平台的脾亲和力在物种之间得以保留。

更新日期:2024-07-31
down
wechat
bug