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化学编程的激活STING的纳米脂质体囊泡可以提高抗癌免疫力

Xiaona Chen¹, Fanchao Meng¹, Yiting Xu¹

¹The First Affiliated Hospital, NHC Key Laboratory of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, 310003, Hangzhou, Zhejiang Province, P. R. China.

Nature communications

|July 31, 2023

概括

新的脂肪体STING激动剂 (SAProsomes) 通过向瘤微环境 (TME) 来增强抗瘤免疫力. 这种方法改善了药物输送,降低了毒性,并在小鼠癌症模型中促进了持久的缓解.

科学领域:

免疫学免疫学免疫学
药物运输药物运输药物运输
在瘤学瘤学.

背景情况:

瘤微环境 (TME) 通常会抑制免疫反应,限制癌症免疫疗法的有效性,如检查点封锁.
激活STING通路可以增强抗瘤免疫力,但系统性输送面临着非目标炎症的挑战.

研究的目的:

开发新的,有针对性的STING激动疗法,以克服TME介导的免疫抑制.
提高STING激动剂的输送和安全性,以改善癌症治疗.

主要方法:

基于STING激动剂MSA-2的以酶激活的前药物产生.
将前药物纳入脂肪体囊泡 (SAProsomes) 进行静脉注射.
在同基因小鼠瘤模型中对SAProsomes的有效性查,评估免疫刺激和治疗结果.

主要成果:

与免费的前药物相比,脂质体输送 (SAProsomes) 改善了药物动力学特性和免疫刺激能力.
治疗成功与增强向瘤和淋巴细胞区分的输送相关.
主要候选人SAProsome-3在乳腺癌和黑色素瘤模型中诱导了强烈的炎症性细胞因子分泌,瘤杀伤性免疫景观和持久的瘤缓解.
SAProsome-3 减少了转移负担,并证明了术后无瘤存活,没有显著的全身毒性.

结论:

SAProsomes代表了针对性和更安全的STING激动剂治疗的原则证明.
这种脂质体输送系统通过改善瘤向和减少全身副作用来提高STING激动剂的疗效.
这些发现支持SAProsomes作为各种癌症的新型免疫治疗策略的潜力.

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