title: Targeted delivery of dendritic polyglycerol-doxorubicin conjugates by scFv-SNAP fusion protein suppresses EGFR+ cancer cell growth.
abstract: Development of effective polymer-based nanocarriers for the successful application in cancer therapy still remains a great challenge in current research. In the present study we present a dendritic polyglycerol-based multifunctional drug immunoconjugate that specifically targets and kills cancer cell lines expressing epidermal growth factor receptor (EGFR). The nanocarrier was provided with a dendritic core as a multifunctional anchoring point, doxorubicin (Doxo) coupled through a pH-sensitive linker, a fluorescence marker, poly(ethylene glycol), as solubilizing and shielding moiety, and a scFv antibody conjugated through the SNAP-Tag technology. The study provides the proof of principle that SNAP-tag technology can be used to generate drug-carrying nanoparticles efficiently modified with single-chain antibodies to specifically target and destroy cancer cells.
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital RWTH Aachen, Germany.
authors.forename: Ahmad Fawzi
authors.initials: AF
authors.lastname: Hussain
authors.forename: Harald Rune
authors.initials: HR
authors.lastname: Krüger
authors.forename: Florian
authors.initials: F
authors.lastname: Kampmeier
authors.forename: Tim
authors.initials: T
authors.lastname: Weissbach
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Felix
authors.initials: F
authors.lastname: Kratz
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.forename: Marcelo
authors.initials: M
authors.lastname: Calderón
authors.forename: Stefan
authors.initials: S
authors.lastname: Barth
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000737:chemistry; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D057127:Single-Chain Antibodies / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C064976:O(6)-benzylguanine; D006147:Guanine; D004317:Doxorubicin; D019853:O(6)-Methylguanine-DNA Methyltransferase