Quantifying the Ligand-Coated Nanoparticle Delivery to Cancer Cells in Solid Tumors
| Autor: | Qin Dai, Stefan Wilhelm, Yih Yang Chen, Warren C. W. Chan, Ding Ding, Shrey Sindhwani, Abdullah Muhammad Syed, Presley MacMillan, Yuwei Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
General Physics and Astronomy
Nanoparticle 02 engineering and technology Ligands 010402 general chemistry 01 natural sciences Flow cytometry Extracellular matrix Mice Antineoplastic Agents Immunological Drug Delivery Systems In vivo Trastuzumab medicine Animals Humans General Materials Science Cell Proliferation Ovarian Neoplasms Drug Carriers Tumor microenvironment medicine.diagnostic_test Chemistry General Engineering Cancer Neoplasms Experimental Silicon Dioxide 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences 3. Good health Cancer cell Cancer research Nanoparticles Female Gold 0210 nano-technology medicine.drug |
| Zdroj: | ACS Nano. 12:8423-8435 |
| ISSN: | 1936-086X 1936-0851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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