Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics

Yifan Wang, Weiye Deng, Dae Yong Lee, Long Yan, Yifei Lu, Shiyan Dong, Kristin Huntoon, Abin Antony, Xuefeng Li, Rui Ye, Yan Zhao, Feiyan Zhao, Benjamin R. Schrank, Jong Hoon Ha, Minjeong Kang, Mingming Yang, Ping Gong, Philip L. Lorenzi, Lin Tan, Thomas D. GallupSarah K. Tang, Zhaogang Yang, Jing Li, Nina N. Sanford, Hongmei Wang, Betty Y.S. Kim, Wen Jiang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)255-263
Number of pages9
JournalNature Nanotechnology
Volume19
Issue number2
DOIs
StatePublished - Feb 2024

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • General Materials Science
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource

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