Regulating Glucose Metabolism with Prodrug Nanoparticles for Promoting Photoimmunotherapy of Pancreatic Cancer
文献类型：期刊论文
| 作者 | Sun, Fang1,2,3; Zhu, Qiurong2,3; Li, Tianliang2,3; Saeed, Madiha2,3; Xu, Zhiai4; Zhong, Feisheng2,3; Song, Rundi2,3; Huai, Manxiu1; Zheng, Mingyue2,3 ; Xie, Cen2,3
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| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 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. |
| WOS关键词 | GUIDED PHOTODYNAMIC THERAPY ; RESISTANCE ; MICROENVIRONMENT ; PEMBROLIZUMAB ; CHEMOTHERAPY ; INHIBITION ; RECURRENCE ; ANTIBODY |
| 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研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000604282900001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296294]  |
| 专题 | 新药研究国家重点实验室 |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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