MYC RNAi-PT Combination Nanotherapy for Metastatic Prostate Cancer Treatment
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1034667
Entities
People
- Angelo M De Marzo
- Charles J Bieberich
- Jinjun Shi
- Omid C. Farokhzad
- Srinivasan Yegnasubramanian
Organizations
- Johns Hopkins University