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 proofof- 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.
Bibliographical noteFunding Information:
NPG was supported by the Children's Cancer Research Fund. PMG was supported by NIH Grant 5K08CA154782-02. This work was supported by a Leukemia & Lymphoma Society New Idea Award (PMG), the Timothy O'Connell Foundation (PMG), and the Children's Cancer Research Fund (PMG). This work also utilized the University of Minnesota Masonic Cancer Center shared flow cytometry and comparative pathology resources, which are supported in part by NIH P30 CA77598.
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- Drug delivery
- Gold nanoparticles
- Molecularly targeted therapy