title: Non-viral gene delivery nanoparticles based on poly(β-amino esters) for treatment of glioblastoma.
abstract: Glioblastoma (GB) is currently characterized by low survival rates and therapies with insufficient efficacy. Here, we describe biodegradable polymers that can deliver genes to primary GB cells as well as GB tumor stem cells in vitro with low non-specific toxicity and transfection efficiencies of up to 60.6 ± 5% in normal (10%) serum conditions. We developed polymer-DNA nanoparticles that remained more stable in normal serum and could also be stored for at least 3 months in ready-to-use form with no measurable decrease in efficacy, expanding their potential in a practical or clinical setting. A subset of polymers was identified that shows a high degree of specificity to tumor cells compared with healthy astrocytes and human neural stem cells when cultured (separately or in co-culture), yielding higher transfection in GB cells while having little to no apparent effect on healthy cells.
authors.affiliation: Department of Biomedical Engineering and the Institute for NanoBioTechnology, Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.
authors.forename: Stephany Y
authors.initials: SY
authors.lastname: Tzeng
authors.forename: Hugo
authors.initials: H
authors.lastname: Guerrero-Cázares
authors.forename: Elliott E
authors.initials: EE
authors.lastname: Martinez
authors.forename: Joel C
authors.initials: JC
authors.lastname: Sunshine
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Green
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D003451:Cryoprotective Agents / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism; D005612:Freeze Drying / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D018014:Gene Transfer Techniques; D005909:Glioblastoma / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D013395:Sucrose / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D000097573:Red Fluorescent Protein
chemical_list: D002232:Carbocyanines; D003451:Cryoprotective Agents; D004247:DNA; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011108:Polymers; D013395:Sucrose; D000097573:Red Fluorescent Protein; C089187:cyanine dye 3; C485184:enhanced green fluorescent protein; C507253:poly(beta-amino ester)