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Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery.

ABSTRACT: Intracellular processes, including endosomal escape and intracellular release, are efficiency-determining steps in achieving successful gene delivery. It has been found that the presence of acid-labile units in polymers can facilitate endosomal escape and that the presence of reducible units in polymers can lead to intracellular release. In this study, poly(amido amine)s with both bioreducible and acid-labile properties were synthesized to improve gene delivery compared with single-responsive carriers. Transfection and cytotoxicity were evaluated in three cell lines. The complexes of DNA with dual-responsive polymers showed higher gene transfection efficiency than single-responsive polymers and polyethylenimine. At the same time, these polymers were tens of times less cytotoxic than polyethylenimine. Therefore, a polymer that is both reducible and acid-labile is a promising material for efficient and biocompatible gene delivery.

SUBMITTER: Yu ZQ

PROVIDER: S-EPMC3511192 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery.

Yu Zhi-Qiang ZQ Yan Jun-Jie JJ You Ye-Zi YZ Zhou Qing-Hui QH

International journal of nanomedicine 20121123

Intracellular processes, including endosomal escape and intracellular release, are efficiency-determining steps in achieving successful gene delivery. It has been found that the presence of acid-labile units in polymers can facilitate endosomal escape and that the presence of reducible units in polymers can lead to intracellular release. In this study, poly(amido amine)s with both bioreducible and acid-labile properties were synthesized to improve gene delivery compared with single-responsive ca ...[more]

PMID: 23209367

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Project description:A family of bioreducible poly(disulfide amine)s, which differ in the length of polymethylene spacer [-(CH(2))(n)-] in the main chain and the side chain, has been synthesized. These bioreducible poly(disulfide amine)s exhibit local environment specific degradability and are associated with lower cytotoxicity than branched poly(ethylenimine) (bPEI, 25 kDa). These cationic polymers also show higher buffering capacity and protonation degree than bPEI, facilitating the endosomal escape of carried genetic materials. The transfection efficiency of these agents is oligomethylene length dependent. Poly(cystaminebisacrylamide-spermine) [poly(CBA-SP)], poly(cystaminebisacrylamide-bis(3-aminopropyl)-1,3-propanediamine) [poly(CBA-APPD)], and poly(cyxtaminebisacrylamide-bis(3-aminopropyl)-ethylenediamine) [ploy(CBA-APED)] with longer propylene [-(CH(2))(3)-] side spacer, demonstrate higher transfection efficacy than the counterpart poly(cystaminebisacrylamide-bis(2-aminoethyl)-1,3-propanediamine) [poly(CBA-AEPD)] and poly(cystaminebisacrylamide-triethylenetetramine) [poly(CBA-TETA)], which have shorter ethylene [-(CH(2))(2)-] side spacer. The poly(CBA-SP), poly(CBA-APPD), poly(CBA-APED) with the main chain spacer of -(CH(2))(4)-, -(CH(2))(3)-, -(CH(2))(2)- demonstrate similar transfection efficiency, indicating the length of polymer main chain spacer has less influence on transfection efficiency. However, with the same short ethylene [-(CH(2))(2)-] side spacer, poly(CBA-AEPD), with the longer main chain oligomethylene units [-(CH(2))(3)-], showed relatively higher transfection efficiency than poly(CBA-TETA), having shorter main chain oligomethylene units [-(CH(2))(2)-]. Of these polymeric carriers, poly(CBA-SP) demonstrated the highest transfection in the C2C12 cell line, while poly(CBA-APED) showed the highest transfection in the HeLa cell line. All of these agents showed greater transfection activity than commercialized bPEI 25 kDa. The poly(disulfide amine)s are promising safe and efficient non-viral vectors for gene delivery.

Dataset Information

Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery.

Publications

Bioreducible and acid-labile poly(amido amine)s for efficient gene delivery.

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