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Updated: May 22, 2026

Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging
Published on: June 21, 2011
Receptor-mediated transcytosis: a mechanism for active extravascular transport of nanoparticles in solid tumors
Wei Lu1, Chiyi Xiong, Rui Zhang
1Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
Targeted nanoparticle-based delivery systems have been used extensively to develop effective cancer theranostics. However, how targeting ligands affect extravascular transport of nanoparticles in solid tumors remains unclear. Here, we show, using B16/F10 melanoma cells expressing melanocortin type-1 receptor (MC1R), that the nature of targeting ligands, i.e., whether they are agonists or antagonists, directs tumor uptake and intratumoral distribution after extravasation of nanoparticles from tumor vessels into the extravascular fluid space. Pegylated hollow gold nanospheres (HAuNS, diameter=40 nm) coated with MC1R agonist are internalized upon ligand-receptor binding, whereas MC1R antagonist-conjugated HAuNS remain attached on the cell surface. Transcellular transport of agonist-conjugated HAuNS was confirmed by a multilayer tumor cell model and by transmission electron microscopy. MC1R agonist- but not MC1R antagonist-conjugated nanoparticles exhibit significantly higher tumor uptake than nontargeted HAuNS and are quickly dispersed from tumor vessels via receptor-mediated endocytosis and subsequent transcytosis. These results confirm an active transport mechanism that can be used to overcome one of the major biological barriers for efficient nanoparticle delivery to solid tumors.
Insights
Targeting ligand type influences nanoparticle delivery in tumors. Agonist-conjugated nanoparticles actively transport into tumors, enhancing uptake via receptor-mediated endocytosis and transcytosis.
Area of Science:
- Nanomedicine
- Cancer Theranostics
- Tumor Biology
Background:
- Targeted nanoparticles are crucial for cancer theranostics.
- Extravascular transport of nanoparticles in tumors is not fully understood.
- Targeting ligands may influence nanoparticle distribution within tumors.
Purpose of the Study:
- To investigate how targeting ligand type (agonist vs. antagonist) affects nanoparticle extravascular transport and tumor uptake.
- To elucidate the mechanism of nanoparticle transport across tumor tissues.
Main Methods:
- Utilized B16/F10 melanoma cells expressing melanocortin type-1 receptor (MC1R).
- Conjugated MC1R agonist or antagonist ligands to pegylated hollow gold nanospheres (HAuNS).
- Employed multilayer tumor cell models and transmission electron microscopy to study nanoparticle transport.
Main Results:
- MC1R agonist-conjugated HAuNS were internalized via receptor-mediated endocytosis and transcytosis.
- MC1R antagonist-conjugated HAuNS remained cell-surface bound.
- Agonist-conjugated nanoparticles showed significantly higher tumor uptake than non-targeted HAuNS.
Conclusions:
- The nature of targeting ligands actively directs nanoparticle uptake and intratumoral distribution.
- Receptor-mediated endocytosis and transcytosis facilitate nanoparticle transport, overcoming biological barriers in solid tumors.
- This active transport mechanism enhances nanoparticle delivery for cancer theranostics.
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