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ACS Nano. 2018 Aug 28;12(8):8423-8435. doi: 10.1021/acsnano.8b03900. Epub 2018 Jul 26.

Quantifying the Ligand-Coated Nanoparticle Delivery to Cancer Cells in Solid Tumors.

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Institute of Biomaterials and Biomedical Engineering , University of Toronto , 164 College Street , Toronto , Ontario M5S 3G9 , Canada.
Stephenson School of Biomedical Engineering , University of Oklahoma , 101 David L. Boren Boulevard , Norman , Oklahoma 73019 , United States.
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine , Hunan University , Changsha 410082 , China.
Departments of Chemistry, Materials Science and Engineering, and Chemical Engineering , University of Toronto , 164 College Street , Toronto , Ontario M5S 3G9 , Canada.
Donnelly Center for Cellular and Biomolecular Research , University of Toronto , 160 College Street , Toronto , Ontario M5S 3E1 , Canada.


Coating the nanoparticle surface with cancer cell recognizing ligands is expected to facilitate specific delivery of nanoparticles to diseased cells in vivo. While this targeting strategy is appealing, no nanoparticle-based active targeting formulation for solid tumor treatment had made it past phase III clinical trials. Here, we quantified the cancer cell-targeting efficiencies of Trastuzumab (Herceptin) and folic acid coated gold and silica nanoparticles in multiple mouse tumor models. Surprisingly, we showed that less than 14 out of 1 million (0.0014% injected dose) intravenously administrated nanoparticles were delivered to targeted cancer cells, and that only 2 out of 100 cancer cells interacted with the nanoparticles. The majority of the intratumoral nanoparticles were either trapped in the extracellular matrix or taken up by perivascular tumor associated macrophages. The low cancer cell targeting efficiency and significant uptake by noncancer cells suggest the need to re-evaluate the active targeting process and therapeutic mechanisms using quantitative methods. This will be important for developing strategies to deliver emerging therapeutics such as genome editing, nucleic acid therapy, and immunotherapy for cancer treatment using nanocarriers.


cancer nanomedicine; flow cytometry; nanoparticle; targeting; tumor microenvironment

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