Hepatocellular Carcinoma Growth Retardation and PD-1 Blockade Therapy Potentiation with Synthetic High-density Lipoprotein

Nano Letters
Junyang WangYaping Li

Abstract

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...Continue Reading

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Citations

May 20, 2020·Acta Pharmacologica Sinica·Bo SunAndrew Z Wang
Mar 28, 2021·Journal of Translational Medicine·Mingxing XuYunbiao Ling
May 22, 2021·Journal of Cellular Physiology·Tan-Jun ZhaoLi Qin
Jun 5, 2021·Journal of Biomedical Nanotechnology·Hongbo NiMeng Niu
Jun 3, 2021·Biomedicines·Athina Trakaki, Gunther Marsche

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