Nanotandem-rocket releases messenger to disrupt metabolic communication for antitumor immunotherapy  

作　　者：Henan Zhao Yuyan Zou Wei Wang Yihong Liu Yuqing Li Bowen Jin Jianghua Li Wansong Chen You-Nian Liu 

机构地区：[1]Hunan Provincial Key Laboratory of Micro&Nano Materials Interface Science,College of Chemistry and Chemical Engineering,Central South University,Changsha 410083,China

出　　处：《Nano Research》2023年第5期7095-7107,共13页纳米研究（英文版）

基　　金：the National Natural Science Foundation of China(No.21807117);Hunan Provincial Science and Technology Plan Project(No.2019TP1001);Hunan Provincial Natural Science Foundation of China(Nos.2022JJ20052 and 2021JJ30788);Central South University Innovation-Driven Research Programme(No.2023CXQD021)。

摘　　要：Metabolic communication between intracellular metabolism and extracellular microenvironment is responsible for celluar metabolism balance and cell survival.Tumor cells adaptively regulate metabolic communication to promote hyperproliferation and immunosuppression.Herein,nanotandem-rockets(hyaluronic acid modified Mg_(5)(CO_(3))_(4)(OH)_(2)(H-MCH))are developed for stepwisely disrupting metabolic communication to activate antitumor immunity.Benefiting from the nanotandem-rocket structure,H-MCH nanoplates successively disrupt the extracellular metabolite transport and intracellular carbohydrate metabolism.Theoretical simulation together with metabolomic analysis discloses the underlying mechanism of H-MCH nanotandem-rockets.The extra-/intra-celluar interruption of metabolic communication provides H-MCH nanotandem-rockets with high efficiency in tumor eradication.Moreover,the interference of metabolic communication reverses immunosuppression to facilitate the intratumoral infiltration of immune cells.With H-MCH nanotandem-rockets as an in situ vaccine,systemic antitumor immunity and immune memory effect are fabricated to eliminate tumor metastasis and recurrence.Different from traditional metabolic poisons(e.g.,arsenic or cyanide),the structure of nanotandem-rockets endows chemical messengers with selective regulation to tumor metabolic communication,but with minimal influence to normal tissues.The nanotandem-rockets provide a powerful paltform to augment the regulating actitiy of chemical messengers in metabolic communication.We expect our discovery of disrupting tumor metabolic communication with chemical messengers will be a powerful strategy for tumor therapy with vast practical applications.

关 键 词：nanotandem-rockets metabolic communication MESSENGER carbohydrate metabolism antitumor immunotherapy 

分 类 号：R730.51[医药卫生—肿瘤] TB383[医药卫生—临床医学]