title: The effect and role of carbon atoms in poly(β-amino ester)s for DNA binding and gene delivery.
abstract: Polymeric vectors for gene delivery are a promising alternative for clinical applications, as they are generally safer than viral counterparts. Our objective was to further our mechanistic understanding of polymer structure-function relationships to allow the rational design of new biomaterials. Utilizing poly(β-amino ester)s (PBAEs), we investigated polymer-DNA binding by systematically varying the polymer molecular weight, adding single carbons to the backbone and side chain of the monomers that constitute the polymers, and varying the type of polymer end group. We then sought to correlate how PBAE binding affects the polyplex diameter and ζ potential, the transfection efficacy, and its associated cytotoxicity in human breast and brain cancer cells in vitro. Among other trends, we observed in both cell lines that the PBAE-DNA binding constant is biphasic with the transfection efficacy and that the optimal values of the binding constant with respect to the transfection efficacy are in the range (1-6) × 10(4) M(-1). A binding constant in this range is necessary but not sufficient for effective transfection.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Bishop
authors.forename: Tiia-Maaria
authors.initials: TM
authors.lastname: Ketola
authors.forename: Stephany Y
authors.initials: SY
authors.lastname: Tzeng
authors.forename: Joel C
authors.initials: JC
authors.lastname: Sunshine
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
authors.forename: Helge
authors.initials: H
authors.lastname: Lemmetyinen
authors.forename: Elina
authors.initials: E
authors.lastname: Vuorimaa-Laukkanen
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Green
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; C507253:poly(beta-amino ester); D002244:Carbon; D004247:DNA