Journal
ONCOTARGET
Volume 7, Issue 25, Pages 38243-38256Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9430
Keywords
gold nanoparticles; drug delivery; leukemia; molecularly targeted therapy; anti-sense
Categories
Funding
- Children's Cancer Research Fund
- NIH [5K08CA154782-02, P30 CA77598]
- Leukemia & Lymphoma Society New Idea Award
- Timothy O'Connell Foundation
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We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.
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