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Updated: Jul 16, 2025
A Comprehensive Procedure to Evaluate the In Vivo Performance of Cancer Nanomedicines
Published on: March 4, 2017
Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics
Yifan Wang1, Weiye Deng1, DaeYong Lee2
1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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.
Insights
Cancer nanomedicine works better in older individuals due to age-related changes in liver cells. This study identifies the scavenger receptor MARCO as a key factor in nanoparticle clearance, suggesting age-tailored treatments.
Area of Science:
- Nanomedicine
- Immunology
- Gerontology
Background:
- Clinical use of nanomedicines is limited by poorly understood hepatic uptake and clearance.
- Cancer nanomedicine efficacy can be influenced by patient age, but the underlying mechanisms are unclear.
Purpose of the Study:
- To investigate the age-associated disparity in cancer nanomedicine efficacy.
- To identify the cellular and molecular mechanisms responsible for age-related differences in nanotherapeutic clearance.
Main Methods:
- Comparative analysis of nanomedicine delivery and efficacy in young versus aged mice.
- Transcriptomic and proteomic analysis of hepatic macrophages.
- Functional studies involving blockade of the scavenger receptor MARCO.
Main Results:
- Tumor delivery and therapeutic outcomes of nanomedicines are superior in aged mice compared to young mice.
- An age-associated decrease in hepatic macrophages expressing the scavenger receptor MARCO was observed across species.
- Blocking MARCO reduced nanoparticle uptake and enhanced anti-tumor effects in young mice, but not in aged mice.
Conclusions:
- Age-related changes in hepatic macrophage function, specifically reduced MARCO expression, impact nanotherapeutic clearance and efficacy.
- These findings highlight an age-associated disparity in nanomedicine pharmacokinetics and pharmacodynamics.
- An age-appropriate strategy is needed for optimizing cancer nanomedicine treatments.
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