A prodrug nanoplatform via esterification of STING agonist and IDO inhibitor for synergistic cancer immunotherapy
作者机构：International Institutes of Medicinethe Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated HospitalZhejiang University School of MedicineKey Laboratory of Respiratory Disease of Zhejiang ProvinceHangzhou 310009China
出 版 物：《Nano Research》 (纳米研究（英文版）)
年 卷 期：2022年第15卷第10期
页 面：9215-9222页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(Nos.81920108001 and 81870007) Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents
主 题：prodrug esterase-responsive immunotherapy stimulator of interferon genes(STING) indoleamine 2 3 dioxygenase(IDO)
摘 要：Cancer immunotherapy has made significant progress in the last few decades,revolutionizing ***,low patient response rates and potential immune-related adverse events continue to be major clinical *** nanomedicine,by virtue of its regulated delivery and modular flexibility,has shown the potential to strengthen antitumor immune responses and sensitize tumors to *** this study,we developed tumor microenvironment(TME)responsive nanomedicine to achieve specific and localized amplification of the immune response in tumor tissue in a safe and effective manner,while simultaneously reducing immune-related side *** synthesized the TME responsive prodrug by coupling MSA-2,a stimulator of interferon genes(STING)agonist,and NLG-919,an indoleamine 2,3 dioxygenase(IDO)*** prodrug was assembled into nanoparticles to enhance the solubility and *** synthesizing a TME responsive prodrug,we aim to explore the therapeutic efficacy of combined regimen(STING agonist and IDO inhibitor)for cancer,and reduce the unwanted side effects of STING agonism on normal *** prodrug and nanoparticles were characterized by mass spectrometry,dynamic light scattering(DLS),and transmission electron microscopy(TEM).Following that,we investigated the tumor accumulation,anti-tumor activity,and toxicity in vitro and in *** nanoparticles demonstrated the ability to inhibit the tumor growth and activate antitumor immune response by modulating immune cells populations in tumor *** TME responsive nanomedicine provided an effective tool for precise targeting,promoting antitumor immunity,and efficient tumor growth inhibition with *** of this study may have implications for future clinical trials.
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