Accession Number:

AD1034668

Title:

MYC RNAi-PT Combination Nanotherapy for Metastatic Prostate Cancer Treatment

Descriptive Note:

Technical Report,01 Sep 2015,29 Sep 2016

Corporate Author:

MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD BALTIMORE United States

Report Date:

2016-10-01

Pagination or Media Count:

27.0

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 RNA seq. We further demonstrate MYC silencing in BMPC cell line-based allograft tumors by the hybrid NPs.

Subject Categories:

  • Medicine and Medical Research
  • Biochemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE