期刊
ACS NANO
卷 12, 期 8, 页码 8423-8435出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b03900
关键词
targeting; nanoparticle; flow cytometry; tumor microenvironment; cancer nanomedicine
类别
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Ontario Graduate Scholarship (OGS)
- Canadian Institute of Health Research (CIHR)
- China Scholarship Council
- Canada-Israel Industrial Research and Development Foundation (CIIRDF)
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.
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