Polycefin, a new prototype of a multifunctional nanoconjugate based on poly(beta-L-malic acid) for drug delivery

Bioconjugate Chemistry
Bong-Seop LeeEggehard Holler

Abstract

A new prototype of nanoconjugate, Polycefin, was synthesized for targeted delivery of antisense oligonucleotides and monoclonal antibodies to brain tumors. The macromolecular carrier contains: 1. biodegradable, nonimmunogenic, nontoxic beta-poly(L-malic acid) of microbial origin; 2. Morpholino antisense oligonucleotides targeting laminin alpha4 and beta1 chains of laminin-8, which is specifically overexpressed in glial brain tumors; 3. monoclonal anti-transferrin receptor antibody for specific tissue targeting; 4. oligonucleotide releasing disulfide units; 5. L-valine containing, pH-sensitive membrane disrupting unit(s), 6. protective poly(ethylene glycol); 7. a fluorescent dye (optional). Highly purified modules were conjugated directly with N-hydroxysuccinimidyl ester-activated beta-poly(L-malic acid) at pendant carboxyl groups or at thiol containing spacers via thioether and disulfide bonds. Products were chemically validated by physical, chemical, and functional tests. In vitro experiments using two human glioma cell lines U87MG and T98G demonstrated that Polycefin was delivered into the tumor cells by a receptor-mediated endocytosis mechanism and was able to inhibit the synthesis of laminin-8 alpha4 and beta1 chains at the...Continue Reading

References

Jun 19, 1995·Brain Research·S SkarlatosW M Pardridge
Jan 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·L W SeymourR Duncan
Jan 1, 1993·Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum·K Thorstensen, I Romslo
May 1, 1996·Cell Biology International·K Mineura, M Kowada
Jun 1, 1997·Antisense & Nucleic Acid Drug Development·J Summerton, D Weller
Jun 6, 1998·Nucleic Acids Research·L MologniC Gambacorti-Passerini
Apr 22, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B FriedrichS A Loening
May 29, 1999·Bioconjugate Chemistry·C A LackeyP S Stayton
Sep 2, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·N MurthyA S Hoffman
Jun 6, 2000·Advanced Drug Delivery Reviews·W M Pardridge
Jun 7, 2000·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·J KopecekZ Lu
Oct 13, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J Baselga
Nov 22, 2001·Bioconjugate Chemistry·C Y CheungA S Hoffman
Jan 5, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zheng-Rong LuJindrich Kopecek
Jul 4, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yun ZhangWilliam M Pardridge
Nov 14, 2002·Pharmacological Reviews·Zhong Ming QianKwokping Ho
Feb 5, 2003·Advanced Drug Delivery Reviews·Richard B GreenwaldCharles D Conover
Mar 12, 2003·Advanced Drug Delivery Reviews·Hidenori OtsukaKazunori Kataoka
Mar 12, 2003·Advanced Drug Delivery Reviews·R J Christie, D W Grainger
Apr 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Niren MurthyJean M J Fréchet
May 17, 2003·Nature Reviews. Drug Discovery·Ruth Duncan
Jul 29, 2003·Bioorganic & Medicinal Chemistry Letters·Paula RodriguesFelix Kratz
Dec 23, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A DavidJ Kopecek
Jan 22, 2004·Bioconjugate Chemistry·Serguei V VinogradovAlexander V Kabanov
Feb 26, 2004·Nature Medicine·Ronit Satchi-FainaroJudah Folkman
Apr 7, 2004·Advanced Drug Delivery Reviews·Karel Ulbrich, Vladimír Subr
Apr 20, 2004·Advanced Drug Delivery Reviews·Christopher P Leamon, Joseph A Reddy
Feb 22, 2005·Advanced Drug Delivery Reviews·Aparna Nori, Jindrich Kopecek

❮ Previous
Next ❯

Citations

Apr 14, 2010·Pharmaceutical Research·Rameshwar PatilJulia Y Ljubimova
Aug 30, 2011·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Jae Youn HwangDaniel L Farkas
Oct 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hui DingJulia Y Ljubimova
Dec 25, 2007·Oligonucleotides·Zhaoyang YeRam I Mahato
Oct 31, 2012·International Journal of Molecular Sciences·Rameshwar PatilJulia Y Ljubimova
Apr 22, 2015·International Journal of Molecular Sciences·Hui DingEggehard Holler
Aug 3, 2007·Journal of Drug Targeting·Hui DingJindrich Kopecek
Mar 17, 2009·Drug Development and Industrial Pharmacy·Krassimira YonchevaStoian Miloshev
Jan 1, 2010·Journal of Nanotechnology·José Portilla-AriasEggehard Holler
May 30, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Noora VainionpääIsmo Virtanen
Mar 7, 2008·Macromolecular Bioscience·José A Portilla-AriasSebastián Muñoz-Guerra
Mar 20, 2008·Macromolecular Bioscience·José A Portilla-AriasSebastián Muñoz-Guerra
Jun 7, 2014·Macromolecular Bioscience·Alberto Lanz-LandázuriSebastián Muñoz-Guerra
Jul 28, 2011·Macromolecular Bioscience·Alberto Lanz-LandázuriSebastián Muñoz-Guerra
Aug 14, 2012·Macromolecular Chemistry and Physics·Alberto Lanz-LandázuriSebastián Muñoz-Guerra
May 21, 2020·International Journal of Nanomedicine·Rameshwar PatilEggehard Holler
Aug 1, 2020·Advanced Drug Delivery Reviews·Jindřich Kopeček, Jiyuan Yang
Dec 4, 2020·Trends in Biochemical Sciences·Jianguo ZhangZhimin Tao
Oct 6, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jiyuan Yang, Jindřich Kopeček
Nov 13, 2020·Nanomedicine : Nanotechnology, Biology, and Medicine·Andrei A KramerovAlexander V Ljubimov
Jan 1, 2008·Bioconjugate Chemistry·Hiroki TanisakaShunsaku Kimura
Aug 29, 2006·Drug Discovery Today·Arun K IyerHiroshi Maeda
Mar 9, 2015·ACS Biomaterials Science & Engineering·Bryan B HsuPaula T Hammond
Nov 14, 2006·Biomacromolecules·José A Portilla-AriasSebastian Muñoz-Guerra
Aug 25, 2009·Advanced Drug Delivery Reviews·Ehud Segal, Ronit Satchi-Fainaro
Aug 20, 2011·Biochimica Et Biophysica Acta·Tracy R DanielsManuel L Penichet

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.