Related Experiment Video
Updated: Feb 20, 2026
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting of Nanomaterials
1Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, Henan, 450002, China.
Abstract:
Malignant tumor (cancer) remains as one of the deadliest diseases throughout the world, despite its overall mortality drops. Nanomaterials (NMs) have been widely studied as diagnostic and/or therapeutic agents for tumors. A feature of NMs, compared to small molecules, is that NMs can be concentrated passively in tumors through enhanced permeability and retention (EPR) effect. In the meantime, NMs can be engineered to target toward tumor specific markers in an active manner, e.g., receptor-mediated targeting. The relative contribution of the EPR effect and the receptor-mediated targeting to NM accumulation in tumor tissues has not been clearly defined yet. Here, we tackle this fundamental issue by reviewing previous studies. First, we summarize the current knowledge on these two tumor targeting strategies of NMs, and on how NMs arrive to tumors from blood circulation. We then demonstrate that contribution of the active and passive effects to total accumulation of NMs in tumors varies with time. Over time, the receptor-mediated targeting contributes more than the EPR effect with a ratio of 3 in the case of urokinase-type plasminogen activator receptor (uPAR)-mediated targeting and human serum albumin (HSA)-mediated EPR effect. Therefore, this review highlights the dynamics of active and passive targeting of NMs on their accumulation at tumor sites, and is valuable for future design of NMs in cancer diagnosis and treatment.
Insights
Nanomaterials (NMs) target tumors via passive enhanced permeability and retention (EPR) effect and active receptor-mediated targeting. Active targeting becomes more significant over time, contributing more to NM accumulation in tumors than passive EPR effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Malignant tumors (cancer) represent a significant global health challenge.
- Nanomaterials (NMs) are investigated for cancer diagnosis and therapy.
- NMs can accumulate in tumors via passive enhanced permeability and retention (EPR) effect and active receptor-mediated targeting.
Purpose of the Study:
- To clarify the relative contributions of EPR effect and receptor-mediated targeting to NM accumulation in tumors.
- To review the mechanisms of NM tumor targeting and circulation to tumors.
- To analyze the temporal dynamics of active versus passive NM targeting in tumor tissues.
Main Methods:
- Comprehensive review of existing studies on NM tumor targeting strategies.
- Analysis of NM accumulation in tumors based on passive (EPR) and active (receptor-mediated) mechanisms.
- Comparison of the time-dependent contributions of active and passive targeting.
Main Results:
- The relative contributions of active and passive targeting to NM accumulation in tumors vary over time.
- Receptor-mediated targeting demonstrates a greater contribution than the EPR effect over time.
- A specific example shows active targeting (uPAR-mediated) contributing 3 times more than passive EPR (HSA-mediated) accumulation.
Conclusions:
- The dynamics of active and passive targeting are crucial for understanding NM accumulation at tumor sites.
- This review provides insights into the temporal interplay between different NM targeting strategies.
- Findings are valuable for optimizing the design of NMs for improved cancer diagnosis and treatment.
