title: Immunostimulatory sutures that treat local disease recurrence following primary tumor resection.
abstract: Neuroblastoma is a common childhood cancer that often results in progressive minimal residual disease after primary tumor resection. Cytosine-phosphorothioate-guanine oligonucleotides (CpG ODN) have been reported to induce potent anti-tumor immune responses. In this communication, we report on the development of a CpG ODN-loaded suture that can close up the wound following tumor excision and provide sustained localized delivery of CpG ODN to treat local disease recurrence. The suture was prepared by melt extruding a mixture of polylactic acid-co-glycolic acid (PLGA 75:25 0.47 dL g⁻¹) pellets and CpG ODN 1826. Scanning electron microscopy images showed that the sutures were free of defects and cracks. UV spectrophotometry measurements at 260 nm showed that sutures provide sustained release of CpG ODN over 35 days. Syngeneic female A/J mice were inoculated subcutaneously with 1 × 10⁶ Neuro-2a murine neuroblastoma wild-type cells and tumors were grown between 5 to 10 mm before the tumors were excised. Wounds from the tumor resection were closed using CpG ODN-loaded sutures and/or polyglycolic acid Vicryl suture. Suppression of neuroblastoma recurrence and mouse survival were significantly higher in mice where wounds were closed using the CpG ODN-loaded sutures relative to all other groups.
authors.affiliation: University of Iowa, Iowa City, 52242, USA.
authors.forename: Janjira
authors.initials: J
authors.lastname: Intra
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Robin L
authors.initials: RL
authors.lastname: Williams
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhu
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Sandler
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D019344:Lactic Acid; D008422:Materials Testing; D051379:Mice; D008805:Mice, Inbred A; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000601:surgery* / Q000628:therapy*; D009447:Neuroblastoma / Q000276:immunology / Q000601:surgery / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013537:Sutures
chemical_list: D000276:Adjuvants, Immunologic; D001672:Biocompatible Materials; C408982:CPG-oligonucleotide; D003692:Delayed-Action Preparations; D009838:Oligodeoxyribonucleotides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid