{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang J"],"funding":["NCI NIH HHS","NIH","Department of Defense"],"pagination":["36-44"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4631633"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["218"],"pubmed_abstract":["To develop a biodegradable polymeric drug delivery system for the treatment of ovarian cancer with the capacity for non-invasive fate monitoring, we designed and synthesized N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugates. The polymer backbone was labeled with acceptor fluorophore Cy5, while donor fluorophores (Cy3 or EPI) were attached to HPMA copolymer side chains via an enzyme-cleavable GFLG linker. This design allows elucidating separately the fate of the drug and of the polymer backbone using fluorescence resonance energy transfer (FRET). The degradable diblock conjugate (2P-EPI) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using a bifunctional chain transfer agent (Peptide2CTA). The pharmacokinetics (PK) and therapeutic effect of 2P-EPI (Mw ~100 kDa) were determined in mice bearing human ovarian carcinoma A2780 xenografts. Compared to 1st generation conjugate (P-EPI, Mw <50 kDa), 2P-EPI demonstrated remarkably improved PK such as fourfold terminal half-life (33.22 ± 3.18 h for 2P-EPI vs. 7.55 ± 3.18 h for P-EPI), which is primarily attributed to the increased molecular weight of the polymer carrier. Notably, complete tumor remission and long-term inhibition of tumorigenesis (100 days) were achieved in mice (n=5) treated with 2P-EPI. Moreover, in vitro cell uptake and intracellular drug release were determined via FRET intensity changes. The results establish a solid foundation for future in vivo tracking of drug delivery and chain scission of polymeric conjugates by FRET imaging."],"journal":["Journal of controlled release : official journal of the Controlled Release Society"],"pubmed_title":["FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy."],"pmcid":["PMC4631633"],"funding_grant_id":["CA156933","R42 CA156933","R41 CA156933","W81XWH-13-1-0160"],"pubmed_authors":["Yang J","Radford DC","Zhang R","Kopecek J"],"additional_accession":[]},"is_claimable":false,"name":"FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy.","description":"To develop a biodegradable polymeric drug delivery system for the treatment of ovarian cancer with the capacity for non-invasive fate monitoring, we designed and synthesized N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugates. The polymer backbone was labeled with acceptor fluorophore Cy5, while donor fluorophores (Cy3 or EPI) were attached to HPMA copolymer side chains via an enzyme-cleavable GFLG linker. This design allows elucidating separately the fate of the drug and of the polymer backbone using fluorescence resonance energy transfer (FRET). The degradable diblock conjugate (2P-EPI) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using a bifunctional chain transfer agent (Peptide2CTA). The pharmacokinetics (PK) and therapeutic effect of 2P-EPI (Mw ~100 kDa) were determined in mice bearing human ovarian carcinoma A2780 xenografts. Compared to 1st generation conjugate (P-EPI, Mw <50 kDa), 2P-EPI demonstrated remarkably improved PK such as fourfold terminal half-life (33.22 ± 3.18 h for 2P-EPI vs. 7.55 ± 3.18 h for P-EPI), which is primarily attributed to the increased molecular weight of the polymer carrier. Notably, complete tumor remission and long-term inhibition of tumorigenesis (100 days) were achieved in mice (n=5) treated with 2P-EPI. Moreover, in vitro cell uptake and intracellular drug release were determined via FRET intensity changes. The results establish a solid foundation for future in vivo tracking of drug delivery and chain scission of polymeric conjugates by FRET imaging.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Nov","modification":"2025-04-04T01:18:07.287Z","creation":"2019-03-27T02:01:16Z"},"accession":"S-EPMC4631633","cross_references":{"pubmed":["26410808"],"doi":["10.1016/j.jconrel.2015.09.045"]}}