Faculty, Staff and Student Publications
Publication Date
2-1-2024
Journal
Nature Nanotechnology
DOI
10.1038/s41565-023-01502-3
PMID
37723279
PMCID
PMC12289334
PubMedCentral® Posted Date
7-24-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
Humans, Mice, Animals, Neoplasms, Phagocytes, Nanomedicine, Nanoparticles, Kinetics
Published Open-Access
yes
Recommended Citation
Wang, Yifan; Deng, Weiye; Lee, DaeYong; et al., "Age-Associated Disparity in Phagocytic Clearance Affects the Efficacy of Cancer Nanotherapeutics" (2024). Faculty, Staff and Student Publications. 4549.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4549
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