Poly(methylidene malonate 2.1.2) nanoparticles: A biocompatible polymer that enhances peri-adventitial adenoviral gene delivery

Beiping Qiang, Amit Segev, Isabelle Beliard, Nafiseh Nili, Bradley H. Strauss, Michael V. Sefton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Vascular gene therapy is currently limited by low and transient levels of gene transfection. The objectives of this study were to determine whether peri-adventitial delivery of adenovirus coupled to nanoparticles could improve transfection efficiency and duration. Adenovirus was absorbed to the surface of nanoparticles that were made from poly(methylidene malonate)2.1.2 (PMM2.1.2). These complexes were found to have good adhesive properties to both cultured vascular smooth muscle cells and to the luminal and adventitial layers of excised rabbit carotid arteries. Adenovirus encoding to β-galactosidase coupled to PMM2.1.2 nanoparticles or adenovirus alone were delivered locally to the adventitia of rabbit carotid arteries. Transfection rate was assessed histologically by the percentage of β-galactosidase positive cells in the vessel wall at 1 and at 2 weeks. There was significantly higher transfection rate when adenovirus was complexed with nanoparticles as compared to free adenovirus (At 1 week: 10±3.9% β-gal positive cells vs. 2.4±0.3% and at 2 weeks: 4.3±4.1% vs. 0%, P<0.005 for all). This difference was present in both the medial and adventitial layers. In conclusion, adenoviral mediated gene therapy was significantly enhanced by adsorbing the virus to PMM2.1.2 nanoparticles. This delivery method may be a good therapeutic strategy for the treatment of various vascular diseases.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalJournal of Controlled Release
Issue number3
StatePublished - 27 Aug 2004
Externally publishedYes


  • Adenovirus
  • Gene delivery
  • Nanoparticles


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