Accession Number:

ADA621624

Title:

Circumventing Therapeutic Resistance and the Emergence of Disseminated Breast Cancer Cells Through Non-Invasive Optical Imaging

Descriptive Note:

Annual rept. 1 Jul 2014-30 May 2015

Corporate Author:

DUKE UNIV DURHAM NC

Report Date:

2015-06-01

Pagination or Media Count:

43.0

Abstract:

Herein we explore a series of optically distinct near infrared emissive polymersomes NIREPs biodegradable polymer vesicles that manifest extraordinarily high irradiances and are ideally suited for in vivo optical imaging, each conjugated to different antibodies for the non-invasive molecular imaging of all breast cancer sites within a patient, including micrometastases. In Year 2, we have taken significant steps to optimize NIREP fabrication protocols to ensure antibodies can be reproducibly conjugated to the surface of NIREPs while preserving native antigen-recognition properties. We have developed a fluoronitrobenzoic acid FNB conjugation strategy, which enables us to covalently attach trastuzumab anti-HER2 IgG to the surface of pre-fabricated NIREPs under mild, aqueous conditions. In model experiments, we have demonstrated that covalent modification of trastuzumab does not affect HER2 recognition properties. Furthermore, we have developed a sensitive Western blot protocol for the detection of trastuzumab attached to NIREPs to allow accurate quantification of NIREP surface functionalization density. With our new protocols, we are well placed in Year 3 to generate a cocktail of antibody-functionalized NIREPs for in vitro and in vivo evaluation.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research
  • Optical Detection and Detectors
  • Biomedical Instrumentation and Bioengineering

Distribution Statement:

APPROVED FOR PUBLIC RELEASE