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载药-抗原混合膜包覆纳米混悬剂用于多模式抗脑胶质瘤治疗

Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery.

机构信息

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China.

出版信息

J Nanobiotechnology. 2021 Nov 20;19(1):378. doi: 10.1186/s12951-021-01110-0.

Abstract

BACKGROUND

Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m).

RESULTS

Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n.

CONCLUSION

DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy.

摘要

背景

脑胶质瘤是人类最致命的癌症之一。尽管已经探索了许多治疗脑胶质瘤的策略,但这些策略很少在临床上使用。脑胶质瘤治疗面临的挑战不仅涉及化疗药物和免疫治疗药物的开发,还涉及缺乏一个能够将这两种药物递送到靶向部位的强大平台。在这里,我们基于 C6 细胞膜和 DC 细胞膜开发了化疗免疫治疗药物递送载体,以创建杂交膜包裹的 DTX 纳米混悬剂(DNS-[C6&DC]m)。

结果

结果表明成功实现了杂交膜融合和纳米混悬剂功能化,DNS-[C6&DC]m 可用于不同模式的抗脑胶质瘤治疗。对于药物递送,膜涂层可通过 C6 细胞膜的同源靶向机制应用于靶向源癌细胞。对于癌症免疫治疗,仿生纳米混悬剂能够基于树突状细胞膜(DCm)的专业抗原呈递特性引发免疫反应,DCm 携带完整的癌细胞膜抗原,并促进膜结合肿瘤抗原的摄取,以有效呈递和下游免疫反应。

结论

DNS-[C6&DC]m 是一种多功能仿生纳米药物递送系统,通过肿瘤靶向药物递送与免疫治疗相结合,具有治疗脑胶质瘤的潜力,为多种癌症治疗模式提供了一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88f3/8606100/917fd313bcd6/12951_2021_1110_Fig1_HTML.jpg

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