SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy.
Jordan A NaumannJohn C WidenLeslie A JonartMaryam EbadiJian TangDavid J GordonDaniel A HarkiPeter M GordonPublished in: Bioconjugate chemistry (2018)
The limited delivery of chemotherapy agents to cancer cells and the nonspecific action of these agents are significant challenges in oncology. We have previously developed a customizable drug delivery and activation system in which a nucleic acid functionalized gold nanoparticle (Au-NP) delivers a drug that is selectively activated within a cancer cell by the presence of an mRNA unique to the cancer cell. The amount of drug released from sequestration to the Au-NP is determined by both the presence and the abundance of the cancer cell specific mRNA in a cell. We have now developed this technology for the potent, but difficult to deliver, topoisomerase I inhibitor SN-38. Herein, we demonstrate both the efficient delivery and selective release of SN-38 from gold nanoparticles in Ewing sarcoma cells with resulting efficacy in vitro and in vivo. These results provide further preclinical validation for this novel cancer therapy and may be extendable to other cancers that exhibit sensitivity to topoisomerase I inhibitors.
Keyphrases
- gold nanoparticles
- reduced graphene oxide
- cancer therapy
- drug delivery
- nucleic acid
- cell therapy
- induced apoptosis
- sensitive detection
- single cell
- palliative care
- cell cycle arrest
- adverse drug
- locally advanced
- radiation therapy
- photodynamic therapy
- quantum dots
- oxidative stress
- cell proliferation
- signaling pathway
- wastewater treatment
- cell death
- anti inflammatory
- rectal cancer
- chemotherapy induced
- mass spectrometry
- high resolution
- clinical evaluation
- childhood cancer