Accession Number : ADA613204


Title :   FRET Imaging Trackable Long-Circulating Biodegradable Nanomedicines for Ovarian Cancer Therapy


Descriptive Note : Annual rept. 1 Sep 2013-31 Aug 2014


Corporate Author : UTAH UNIV SALT LAKE CITY


Personal Author(s) : Kopecek, Jindrich


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a613204.pdf


Report Date : Sep 2014


Pagination or Media Count : 21


Abstract : The major goal of the proposed project is to develop a novel FRET imaging strategy, which permits visualizing the biodegradation of copolymer-drug conjugates at the body, tissue and cell levels in real time. The information will initiate the understanding of in vivo behavior of biodegradable polymers and support the design of highly efficient drug delivery systems. In the first year of the project we have synthesized numerous FRET trackable biodegradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates that were labeled with Cy3 and/or Cy5, conjugates that contained epirubicin and performed click reactions for chain extension to manipulate their molecular weight. The conjugates were characterized by physicochemical methods and in vitro using human ovarian carcinoma cells. FRET technique was used to investigate the conjugates at cellular level. We achieved correlation of the FRET signal on one hand with the level of cathepsin B expression and with the intracellular degradation of the conjugates on the other hand. In fluorescence spectrophotometry experiments we have demonstrated a quantitative correlation between the FRET signal and the degradation of the HPMA copolymer conjugates. Thus our hypothesis that FRET imaging is suitable for the determination of the degradation and fate of backbone degradable HPMA copolymer conjugates has been validated at the cellular level.


Descriptors :   *BIODEGRADATION , *OVARIAN CANCER , BEHAVIOR , COPOLYMERS , CORRELATION , DEGRADATION , DETERMINATION , FLUORESCENCE , HYPOTHESES , IMAGES , IN VITRO ANALYSIS , IN VIVO ANALYSIS , METHODOLOGY , MOLECULAR WEIGHT , PHYSICOCHEMICAL PROPERTIES , POLYMERS , SIGNALS , STRATEGY , SYNTHESIS , THERAPY


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE