MYC RNAi-Pt Combination Nanotherapy for Metastatic Prostate Cancer Treatment
Technical Report,30 Sep 2015,29 Sep 2016
Brigham and Womens Hospital Boston United States
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The main objective of this project is to develop an innovative nanotherapy modality by combining platinum Pt chemotherapy and MYC-targeting RNA interference RNAi for more effective treatment of metastatic prostate cancer PCa. In Year 1 of this project, we have made substantial progress and accomplishments under the proposed tasks. We synthesized, characterized and screened a large library of lipid-polymer hybrid NPs for siRNA delivery, by systematically exploring i the effect of organic solvent on the NP formulation ii the effect of surface lipid-PEG on NP behaviors in vitro and in vivo and iii the use of redox-sensitive polymers for triggered siRNA release and enhanced gene silencing. The optimized siRNA NPs showed effective MYC silencing in vitro, as demonstrated by the western blot and immuno-fluorescence results. We also synthesized a series of cisplatin prodrugs as planned for NP encapsulation and in vitro cytotoxicity test. In parallel, we have established cell lines derived from sites of metastasis of MYC-driven transgenic BMPC tumors and performed MYC signature analysis in BMPC mice by RNAseq. We further demonstrate MYC silencing in BMPC cell line-based allograft tumors by the hybrid NPs.
- Medicine and Medical Research