MYC RNAi-PT Combination Nanotherapy for Metastatic Prostate Cancer Treatment
Technical Report,01 Sep 2015,29 Sep 2016
MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD BALTIMORE 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 RNA seq. We further demonstrate MYC silencing in BMPC cell line-based allograft tumors by the hybrid NPs.
- Medicine and Medical Research