Hepatocellular Carcinoma Growth Retardation and PD-1 Blockade Therapy Potentiation with Synthetic High-density Lipoprotein
文献类型：期刊论文
| 作者 | Wang, Junyang1,2; Meng, Jia1,3; Ran, Wei1,3; Lee, Robert J.2,4; Teng, Lesheng1,2; Zhang, Pengcheng1,3 ; Li, Yaping1,3
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| 刊名 | NANO LETTERS
 |
| 出版日期 | 2019-08-01 |
| 卷号 | 19期号:8页码:5266-5276 |
| 关键词 | High-density lipoproteins immunotherapy hepatocellular carcinoma combination therapy thermal ablation |
| ISSN号 | 1530-6984 |
| DOI | 10.1021/acs.nanolett.9b01717 |
| 通讯作者 | Teng, Lesheng(tenglesheng@j1u.edu.cn) ; Zhang, Pengcheng(pzhang@simm.ac.cn) ; Li, Yaping(ypli@simm.ac.cn) |
| 英文摘要 | The long progression-free survival (PFS) of patients with inoperable hepatocellular carcinoma (HCC) tumors is an unmet clinical need. Imaging-guided in situ ablation and vaccination with nanoplatforms could be a promising way to achieve durable disease control and long PFS. In the present work, we show that a biomimetic nanoplatform, namely, synthetic high-density lipoprotein (sHDL), can transport photothermal agent DiR and other drugs preferentially into the cytosol of HCC cells, enabling imaging-guided combination therapy for HCC in vivo. With a single injection, the sHDLs reduced the tumor burden, triggered immunogenic cell death (ICD), promoted dendritic cell (DC) maturation, and induced CD8(+) T cell responses, which together sensitized the tumors to PD-1 blockade. Tumor remission and immune protection were achieved using sHDL loaded with DiR and a stimulator of interferon genes agonist vadimezan, in conjunction with a PD-1 blockade. The replacement of vadimezan with the chemotherapeutic mertansine potentiated ICD of HCC cells, but the drug interfered with DC maturation and subsequent CD8(+) T cell priming, resulting in unsatisfactory disease control. Our work provides a generalizable nanoplatform for the combined photothermal ablation and immunotherapy of HCC and highlights the importance of cancer-cell-specific ICD induction and simultaneous DC activation during in situ vaccination. |
| WOS关键词 | IMMUNOGENIC CELL-DEATH ; CHECKPOINT BLOCKADE ; CANCER ; NANOPARTICLES ; INNATE ; TUMORS ; DELIVERY ; IMMUNOTHERAPY ; HETEROGENEITY ; RECEPTORS |
| 资助项目 | National Natural Science Foundation of China[81690265] ; National Natural Science Foundation of China[31870995] ; National Natural Science Foundation of China[81671808] ; National Natural Science Foundation of China[81630052] ; Youth Innovation Promotion Association of CAS[2017335] ; SA-SIBS Scholarship Program |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
| 语种 | 英语 |
| WOS记录号 | WOS:000481563800058 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288999]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Teng, Lesheng; Zhang, Pengcheng; Li, Yaping |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Ctr Pharmaceut, Shanghai 201203, Peoples R China 2.Jilin Univ, Sch Life Sci, Changchun 130012, Jilin, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Ohio State Univ, Div Pharmaceut & Pharmaceut Chem, Coll Pharm, Columbus, OH 43210 USA |
| 推荐引用方式 GB/T 7714 | Wang, Junyang,Meng, Jia,Ran, Wei,et al. Hepatocellular Carcinoma Growth Retardation and PD-1 Blockade Therapy Potentiation with Synthetic High-density Lipoprotein[J]. NANO LETTERS,2019,19(8):5266-5276. |
| APA | Wang, Junyang.,Meng, Jia.,Ran, Wei.,Lee, Robert J..,Teng, Lesheng.,...&Li, Yaping.(2019).Hepatocellular Carcinoma Growth Retardation and PD-1 Blockade Therapy Potentiation with Synthetic High-density Lipoprotein.NANO LETTERS,19(8),5266-5276. |
| MLA | Wang, Junyang,et al."Hepatocellular Carcinoma Growth Retardation and PD-1 Blockade Therapy Potentiation with Synthetic High-density Lipoprotein".NANO LETTERS 19.8(2019):5266-5276. |
入库方式： OAI收割
来源：上海药物研究所
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