Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer

doi:10.1002/advs.202002746

	Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer
	Sun, Fang 1,2,3; Zhu, Qiurong 2,3; Li, Tianliang 2,3; Saeed, Madiha 2,3; Xu, Zhiai 4; Zhong, Feisheng 2,3; Song, Rundi 2,3; Huai, Manxiu 1; Zheng, Mingyue 2,3; Xie, Cen 2,3
刊名	ADVANCED SCIENCE
	2021-01-04
页码	12
关键词	glucose metabolism immunogenic cell death pancreatic cancer photoimmunotherapy prodrug nanoparticles
DOI	10.1002/advs.202002746
通讯作者	Xu, Leiming(xuleiming@xinhuamed.com.cn) ; Yu, Haijun(hjyu@simm.ac.cn)
英文摘要	The low immunogenicity, insufficient infiltration of T lymphocytes, and dismal response to immune checkpoint blockade therapy pose major difficulties in immunotherapy of pancreatic cancer. Photoimmunotherapy by photodynamic therapy (PDT) can induce an antitumor immune response by triggering immunogenic cell death in the tumor cells. Notwithstanding, PDT-driven oxygen consumption and microvascular damage can further aggravate hypoxia to exaggerates glycolysis, leading to lactate accumulation and immunosuppressive tumor microenvironment. Herein, a supramolecular prodrug nanoplatform codelivering a photosensitizer and a prodrug of bromodomain-containing protein 4 inhibitor (BRD4i) JQ1 for combinatory photoimmunotherapy of pancreatic cancer are demonstrated. The nanoparticles are fabricated by host-guest complexation between cyclodextrin-grafted hyaluronic acid (HA-CD) and adamantine-conjugated heterodimers of pyropheophorbide a (PPa) and JQ1, respectively. HA can achieve active tumor targeting by recognizing highly expressed CD44 on the surface of pancreatic tumors. PPa-mediated PDT can enhance the immunogenicity of the tumor cells and promote intratumoral infiltration of the cytotoxic T lymphocytes. Meanwhile, JQ1 combats PDT-mediated immune evasion through inhibiting expression of c-Myc and PD-L1, which are key regulators of tumor glycolysis and immune evasion. Collectively, this study presents a novel strategy to enhance photoimmunotherapy of the pancreatic cancer by provoking T cells activation and overcoming adaptive immune resistance.
资助项目	National Natural Science Foundation of China[51873228] ; National Natural Science Foundation of China[21675055] ; International Cooperation Project of Science and Technology Commission of Shanghai Municipality[20430711800] ; Natural Science Foundation of Shanghai[19140901602] ; Natural Science Foundation of Shandong Province[ZR2019LZL020] ; China Postdoctoral Science Foundation[2019M661667] ; Shanghai Post-Doctoral Excellence Program[2019116] ; Open Fund of the State Key Laboratory of Drug Research[SIMM2004KF-04]
WOS关键词	GUIDED PHOTODYNAMIC THERAPY ; RESISTANCE ; MICROENVIRONMENT ; PEMBROLIZUMAB ; CHEMOTHERAPY ; INHIBITION ; RECURRENCE ; ANTIBODY
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	WILEY
WOS记录号	WOS:000604282900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296294]
专题	中国科学院上海药物研究所
通讯作者	Xu, Leiming; Yu, Haijun
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gastroenterol, Shanghai 2000092, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 4.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China 5.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Sun, Fang,Zhu, Qiurong,Li, Tianliang,et al. Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer[J]. ADVANCED SCIENCE,2021:12.
APA	Sun, Fang.,Zhu, Qiurong.,Li, Tianliang.,Saeed, Madiha.,Xu, Zhiai.,...&Yu, Haijun.(2021).Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer.ADVANCED SCIENCE,12.
MLA	Sun, Fang,et al."Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer".ADVANCED SCIENCE (2021):12.