ArticleJournal of controlled release : official journal of the Controlled Release Society2015
FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 62 citations in OpenAlex.
- Polymer-based chemo-immunotherapy: Combining immunogenic cell death induction and PD-L1 blockade enhances antitumor immunity in melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- PD-L1 targeted antibody-polymer-Epirubicin conjugate prolongs survival in a preclinical murine model of advanced ovarian cancer.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Hydrophilic biomaterials: From crosslinked and self-assembled hydrogels to polymer-drug conjugates and drug-free macromolecular therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- [Research progress on the fluorescence resonance energy transfer-based polymer micelles as drug carriers].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2022Review
- Nanomedicines in B cell-targeting therapies.Acta biomaterialia · 2022Review
- Review
- Inhibition of Immunosuppressive Tumors by Polymer-Assisted Inductions of Immunogenic Cell Death and Multivalent PD-L1 Crosslinking.Advanced functional materials · 2020Article
- Polymer nanomedicines.Advanced drug delivery reviews · 2020Review
- Fluorescence Imaging as a Tool in Preclinical Evaluation of Polymer-Based Nano-DDS Systems Intended for Cancer Treatment.Pharmaceutics · 2019Review
- A Macromolecular Janus Kinase (JAK) Inhibitor Prodrug Effectively Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.Pharmaceutical research · 2019Article
- The Light at the End of the Tunnel-Second Generation HPMA Conjugates for Cancer Treatment.Current opinion in colloid & interface science · 2017Article
- Backbone Degradable N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates with Gemcitabine and Paclitaxel: Impact of Molecular Weight on Activity toward Human Ovarian Carcinoma Xenografts.Molecular pharmaceutics · 2017Article
- Covalent nano delivery systems for selective imaging and treatment of brain tumors.Advanced drug delivery reviews · 2017Review
- Biodegradable Poly(ester-urethane) Carriers Exhibiting Controlled Release of Epirubicin.Pharmaceutical research · 2017Article
- Diverse Applications of Nanomedicine.ACS nano · 2017Review
- Design of smart HPMA copolymer-based nanomedicines.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Indium-based and iodine-based labeling of HPMA copolymer-epirubicin conjugates: Impact of structure on the in vivo fate.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.