TY - JOUR
T1 - A family of bioreducible poly(disulfide amine)s for gene delivery
AU - Ou, Mei
AU - Xu, Rongzuo
AU - Kim, Sun Hwa
AU - Bull, David A.
AU - Kim, Sung Wan
N1 - Funding Information:
This work is supported by National Institutes of Health (NIH) grant HL065477 (SWK) and HL071541 (DAB). We thank Dr. Zheng-Rong Lu (University of Utah, Salt Lake City, UT) for the generous use of equipments and facilities.
PY - 2009/10
Y1 - 2009/10
N2 - A family of bioreducible poly(disulfide amine)s, which differ in the length of polymethylene spacer [-(CH2)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 [-(CH2)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 [-(CH2)2-] side spacer. The poly(CBA-SP), poly(CBA-APPD), poly(CBA-APED) with the main chain spacer of -(CH2)4-, -(CH2)3-, -(CH2)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 [-(CH2)2-] side spacer, poly(CBA-AEPD), with the longer main chain oligomethylene units [-(CH2)3-], showed relatively higher transfection efficiency than poly(CBA-TETA), having shorter main chain oligomethylene units [-(CH2)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.
AB - A family of bioreducible poly(disulfide amine)s, which differ in the length of polymethylene spacer [-(CH2)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 [-(CH2)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 [-(CH2)2-] side spacer. The poly(CBA-SP), poly(CBA-APPD), poly(CBA-APED) with the main chain spacer of -(CH2)4-, -(CH2)3-, -(CH2)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 [-(CH2)2-] side spacer, poly(CBA-AEPD), with the longer main chain oligomethylene units [-(CH2)3-], showed relatively higher transfection efficiency than poly(CBA-TETA), having shorter main chain oligomethylene units [-(CH2)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.
KW - Biodegradable
KW - Gene delivery
KW - Gene transfection
KW - Poly(disulfide amine)s
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U2 - 10.1016/j.biomaterials.2009.06.050
DO - 10.1016/j.biomaterials.2009.06.050
M3 - Article
C2 - 19615739
AN - SCOPUS:68549090559
VL - 30
SP - 5804
EP - 5814
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 29
ER -