Synthesis and characterization of new poly(ortho ester amidine) copolymers for non-viral gene delivery

Rupei Tang, Weihang Ji, Chun Wang

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45 Scopus citations


A new type of pH-labile cationic polymers, poly(ortho ester amidine) (POEAmd) copolymers, has been synthesized and characterized with potential future application as gene delivery carriers. The acid-labile POEAmd copolymer was synthesized by polycondensation of a new ortho ester diamine monomer with dimethylaliphatimidates, and a non-acid-labile polyamidine (PAmd) copolymer was also synthesized for comparison using a triethylene glycol diamine monomer. Both copolymers were easily dissolved in water, and can efficiently bind and condense plasmid DNA at neutral pH, forming nano-scale polyplexes. The physicochemical properties of the polyplexes have been studied using dynamic light scattering, gel electrophoresis, ethidium bromide exclusion, and heparin competition. The average size of the polyplexes was dependent on the amidine:phosphate (N:P) ratio of the polymers to DNA. Polyplexes containing the acid-labile POEAmd or the non-acid-labile PAmd showed similar average particle size, comparable strength of condensing DNA, and resistance to electrostatic destabilization. They also share similar metabolic toxicity to cells as measured by MTT assay. Importantly, the acid-labile polyplexes undergo accelerated polymer degradation at mildly acid-pHs, resulting in increasing particle size and the release of intact DNA plasmid. Polyplexes from both types of polyamidines caused distinct changes in the scattering properties of Baby Hamster Kidney (BHK-21) cells, showing swelling and increasing intracellular granularity. These cellular responses are uniquely different from other cationic polymers such as polyethylenimine and point to stress-related mechanisms specific to the polyamidines. Gene transfection of BHK-21 cells was evaluated by flow cytometry. The positive yet modest transfection efficiency by the polyamidines (acid-labile and non-acid-labile alike) underscores the importance of balancing polymer degradation and DNA release with endosomal escape. Insights gained from studying such acid-labile polyamidine-based DNA carriers and their interaction with cells may contribute to improved design of practically useful gene delivery systems.

Original languageEnglish (US)
Pages (from-to)921-932
Number of pages12
Issue number4
StatePublished - Feb 17 2011

Bibliographical note

Funding Information:
The financial support to this work is in part by the NIH (Grant R01CA129189 , to C. Wang), the NSF CAREER Award ( BES 0547613 , to C. Wang), the Program for New Century Excellent Talents in University (No. NCET-10-0435 , to R. Tang), the National Natural Science Foundation of China (No. 21004030 , 50873080 , to R. Tang), the Natural Science Foundation of Jiangsu Province of China (No. BK2010145 , to R. Tang), and the Fundamental Research Funds for the Central Universities of China ( JUSRP21013 , to R. Tang).


  • Copolymer
  • Gene delivery
  • Ortho ester


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