PMMA particle-mediated DNA vaccine for cervical cancer.
DNA vaccination is a novel immunization strategy that possesses many potential advantages over other vaccine strategies. One of the major difficulties hindering the clinical application of DNA vaccination is the relative poor immunogenicity of DNA vaccines. Poly(methyl methacrylate) (PMMA) is a synthetic polymer approved by the Food and Drug Administration for certain human clinical applications such as the bone cement. In vivo, PMMA particles are phagocytosable and have the potential to initiate strong immune responses by stimulating the production of inflammatory cytokines. In this study, we synthesized a series of PMMA particles (PMMA 1-5) with different particle sizes and surface charges to test the feasibility of implementing such polymer particles for DNA vaccination. To our knowledge, this is the first report to show that the gene gun can deliver DNA vaccine by propelling PMMA particles mixed with plasmid DNA for cervical cancer. It was found that PMMA 4 particles (particle size: 460 +/- 160 nm, surface charge: +11.5 +/- 1.8 mV) stimulated the highest level of TNF-alpha production by macrophages in vitro and yielded the best result of antitumor protection in vivo. Therefore, our results possess the potential for translation and implementation of polymer particles in gene gun delivering DNA vaccination.
Lou
Pei-Jen
PJ
Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
Cheng
Wen-Fang
WF
Chung
Yi-Chen
YC
Cheng
Che-Yuan
CY
Chiu
Lien-Hua
LH
Young
Tai-Horng
TH
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008422:Materials Testing; D051379:Mice; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D019904:Polymethyl Methacrylate; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use
D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D004247:DNA; D019904:Polymethyl Methacrylate