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 文獻名： Structure and biological activity of pathogen-like synthetic nanomedicines

 

作者： Orsolya L?rincz, MSc a, Enik? R. T?ke, PhD a, Eszter Somogyi, MSc a, Ferenc Horkay, PhD b, Preethi L. Chandran, PhD b, Jack F. Douglas, PhD c, János Szebeni, PhD d, Julianna Lisziewicz, PhD a,e

a Genetic Immunity Kft, Budapest, Berlini u., Hungary

b Section on Tissue Biophysics and Biomimetics, Program in Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

c Polymers Division, National Institute of Standards and Technology, Gaithersburg, MD 20899

d Nanomedicine Research and Education Center, Bay Zoltan Foundation for Applied Research and Semmelweis University, 1089, Budapest, Nagyvárad tér, Hungary

e Genetic Immunity LLC, 8300 Greensboro Drive, Suite 800 Mclean, Virginia, USA

 

摘要：Here we characterize the structure, stability and intracellular mode of action of DermaVir nanomedicine that is under clinical development for the treatment of HIV/AIDS. This nanomedicine comprises pathogen-like pDNA/PEIm nanoparticles (NPs) having the structure and function resembling spherical viruses that naturally evolved to deliver nucleic acids to the cells. Atomic force microscopy demonstrated spherical 100 – 200 nm NPs with a smooth polymer surface protecting the pDNA in the core. Optical absorption determined both the NP structural stability and biological activity relevant to their ability to escape from the endosome and release the pDNA at the nucleus. Salt, pH and temperature influence nanomedicine shelf-life and intracellular stability. This approach facilitates the development of diverse polyplex nanomedicines where the delivered pDNA-expressed antigens induce immune responses to kill infected cells.

 

關鍵詞：Vaccine; Immunotherapy; Immunity; DermaVir