Nanotandem-rocket releases messenger to disrupt metabolic communication for antitumor immunotherapy
作者机构：Hunan Provincial Key Laboratory of Micro&Nano Materials Interface ScienceCollege of Chemistry and Chemical EngineeringCentral South UniversityChangsha 410083China
出 版 物：《Nano Research》 (纳米研究（英文版）)
年 卷 期：2023年第16卷第5期
页 面：7095-7107页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 100214[医学-肿瘤学] 0703[理学-化学] 10[医学] 0702[理学-物理学]
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)。
主 题：nanotandem-rockets metabolic communication messenger carbohydrate metabolism antitumor immunotherapy
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.
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