한빛사논문
- 조회311
Yifan Wang 1,10, Weiye Deng 1,10, DaeYong Lee2,10, Long Yan 3,4,10, Yifei Lu 2,10, Shiyan Dong 1, Kristin Huntoon 2, Abin Antony 1, Xuefeng Li 1, Rui Ye1,5, Yan Zhao 3,4, Feiyan Zhao 3, Benjamin R. Schrank 1, JongHoon Ha1, Minjeong Kang1, Mingming Yang6, Ping Gong 7, Philip L. Lorenzi 8, Lin Tan8, Thomas D. Gallup 2, Sarah K. Tang2, Zhaogang Yang1, Jing Li1, Nina N. Sanford6, Hongmei Wang 3,4 , Betty Y. S. Kim 2,9 & Wen Jiang 1
1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
4University of Chinese Academy of Sciences, Beijing, China.
5The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
6Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
7Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
8Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9The Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
10These authors contributed equally: Yifan Wang, Weiye Deng, DaeYong Lee, Long Yan, Yifei Lu.
Corresponding authors : Correspondence to Hongmei Wang, Betty Y. S. Kim or Wen Jiang.
Abstract
Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger receptor MARCO in mice, non-human primates and humans. Therapeutic blockade of MARCO is shown to decrease the phagocytic uptake of nanoparticles and improve the antitumour effect of clinically approved cancer nanotherapeutics in young but not aged mice. Together, these results reveal an age-associated disparity in the phagocytic clearance of nanotherapeutics that affects their antitumour response, thus providing a strong rationale for an age-appropriate approach to cancer nanomedicine.
논문정보
- Research article
- 2023년 09월 (BRIC 등록일 2023-10-04)
- 국외 연구진
- 의약학 > 면역의학
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