Novel Guanidinylated Bioresponsive Poly(amidoamine)s Designed for Short Hairpin RNA Delivery

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2016 Dec 21

PMID 27994462

Citations 4

Authors

Jiankun Yu

Jinmin Zhang

Haonan Xing

Yanping Sun

Zhen Yang

Tianzhi Yang

Cuifang Cai

Xiaoyun Zhao

Li Yang

Pingtian Ding

Affiliations

Soon will be listed here.

Abstract

Two different disulfide (SS)-containing poly(amidoamine) (PAA) polymers were constructed using guanidino (Gua)-containing monomers (ie, arginine [Arg] and agmatine [Agm]) and ,'-cystamine bisacrylamide (CBA) by Michael-addition polymerization. In order to characterize these two Gua-SS-PAA polymers and investigate their potentials as short hairpin RNA (shRNA)-delivery carriers, pSilencer 4.1-CMV shRNA was chosen as a model plasmid DNA to form complexes with these two polymers. The Gua-SS-PAAs and plasmid DNA complexes were determined with particle sizes less than 90 nm and positive ζ-potentials under 20 mV at nucleic acid:polymer weight ratios lower than 1:24. Bioresponsive release of plasmid DNA was observed from both newly constructed complexes. Significantly lower cytotoxicity was observed for both polymer complexes compared with polyethylenimine and Lipofectamine 2000, two widely used transfection reagents as reference carriers. Arg-CBA showed higher transfection efficiency and gene-silencing efficiency in MCF7 cells than Agm-CBA and the reference carriers. In addition, the cellular uptake of Arg-CBA in MCF7 cells was found to be higher and faster than Agm-CBA and the reference carriers. Similarly, plasmid DNA transport into the nucleus mediated by Arg-CBA was more than that by Agm-CBA and the reference carriers. The study suggested that guanidine and carboxyl introduced into Gua-SS-PAAs polymers resulted in a better nuclear localization effect, which played a key role in the observed enhancement of transfection efficiency and low cytotoxicity. Overall, two newly synthesized Gua-SS-PAAs polymers demonstrated great potential to be used as shRNA carriers for gene-therapy applications.

Citing Articles

Charge neutralized poly(β-amino ester) polyplex nanoparticles for delivery of self-amplifying RNA.

Dastgerdi N, Gumus N, Bayraktutan H, Jackson D, Polra K, McKay P Nanoscale Adv. 2024; 6(5):1409-1422.

PMID: 38419881 PMC: 10898429. DOI: 10.1039/d3na00794d.

"PFH/AGM-CBA/HSV-TK/LIPOSOME-Affibody": Novel Targeted Nano Ultrasound Contrast Agents for Ultrasound Imaging and Inhibited the Growth of ErbB2-Overexpressing Gastric Cancer Cells.

Zhou H, Liu H, Zhang Y, Xin Y, Huang C, Li M Drug Des Devel Ther. 2022; 16:1515-1530.

PMID: 35611358 PMC: 9124479. DOI: 10.2147/DDDT.S351623.

A Ternary Synergistic eNOS Gene Delivery System Based on Calcium Ion and L-Arginine for Accelerating Angiogenesis by Maximizing NO Production.

Zhang G, Han S, Wang L, Yao Y, Chen K, Chen S Int J Nanomedicine. 2022; 17:1987-2000.

PMID: 35530975 PMC: 9075900. DOI: 10.2147/IJN.S363168.

PEI-PEG-Coated Mesoporous Silica Nanoparticles Enhance the Antitumor Activity of Tanshinone IIA and Serve as a Gene Transfer Vector.

Zhu Y, Yue M, Guo T, Li F, Li Z, Yang D Evid Based Complement Alternat Med. 2021; 2021:6756763.

PMID: 34790248 PMC: 8592735. DOI: 10.1155/2021/6756763.

References

Kim T, Ou M, Lee M, Kim S . Arginine-grafted bioreducible poly(disulfide amine) for gene delivery systems. Biomaterials. 2008; 30(4):658-64. PMC: 2642962. DOI: 10.1016/j.biomaterials.2008.10.009. View

Li Y, Zhao L, Sun H, Yu J, Li N, Liang J . Gene silencing of FANCF potentiates the sensitivity to mitoxantrone through activation of JNK and p38 signal pathways in breast cancer cells. PLoS One. 2012; 7(8):e44254. PMC: 3429446. DOI: 10.1371/journal.pone.0044254. View

Lin C, Zhong Z, Lok M, Jiang X, Hennink W, Feijen J . Novel bioreducible poly(amido amine)s for highly efficient gene delivery. Bioconjug Chem. 2007; 18(1):138-45. DOI: 10.1021/bc060200l. View

Maskell D, Renault L, Serrao E, Lesbats P, Matadeen R, Hare S . Structural basis for retroviral integration into nucleosomes. Nature. 2015; 523(7560):366-9. PMC: 4530500. DOI: 10.1038/nature14495. View

Kim T, Kim S . Bioreducible polymers for gene delivery. React Funct Polym. 2011; 71(3):344-349. PMC: 3079258. DOI: 10.1016/j.reactfunctpolym.2010.11.016. View

Piest M, Engbersen J . Effects of charge density and hydrophobicity of poly(amido amine)s for non-viral gene delivery. J Control Release. 2010; 148(1):83-90. DOI: 10.1016/j.jconrel.2010.07.109. View

Yin H, Kanasty R, Eltoukhy A, Vegas A, Dorkin J, Anderson D . Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014; 15(8):541-55. DOI: 10.1038/nrg3763. View

Martello F, Piest M, Engbersen J, Ferruti P . Effects of branched or linear architecture of bioreducible poly(amido amine)s on their in vitro gene delivery properties. J Control Release. 2012; 164(3):372-9. DOI: 10.1016/j.jconrel.2012.07.029. View

Wang M, Hu H, Sun Y, Qiu L, Zhang J, Guan G . A pH-sensitive gene delivery system based on folic acid-PEG-chitosan - PAMAM-plasmid DNA complexes for cancer cell targeting. Biomaterials. 2013; 34(38):10120-32. DOI: 10.1016/j.biomaterials.2013.09.006. View

10.

Merdan T, Callahan J, Petersen H, Kunath K, Bakowsky U, Kopeckova P . Pegylated polyethylenimine-Fab' antibody fragment conjugates for targeted gene delivery to human ovarian carcinoma cells. Bioconjug Chem. 2003; 14(5):989-96. DOI: 10.1021/bc0340767. View

11.

Chen J, Qiu X, Ouyang J, Kong J, Zhong W, Xing M . pH and reduction dual-sensitive copolymeric micelles for intracellular doxorubicin delivery. Biomacromolecules. 2011; 12(10):3601-11. DOI: 10.1021/bm200804j. View

12.

van der Aa L, Vader P, Storm G, Schiffelers R, Engbersen J . Optimization of poly(amido amine)s as vectors for siRNA delivery. J Control Release. 2010; 150(2):177-86. DOI: 10.1016/j.jconrel.2010.11.030. View

13.

Naldini L . Gene therapy returns to centre stage. Nature. 2015; 526(7573):351-60. DOI: 10.1038/nature15818. View

14.

Kowal P, Gurtan A, Stuckert P, DAndrea A, Ellenberger T . Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex. J Biol Chem. 2006; 282(3):2047-55. DOI: 10.1074/jbc.M608356200. View

15.

Arote R, Jiang H, Kim Y, Cho M, Choi Y, Cho C . Degradable poly(amido amine)s as gene delivery carriers. Expert Opin Drug Deliv. 2011; 8(9):1237-46. DOI: 10.1517/17425247.2011.586333. View

16.

Li J, Manickam D, Chen J, Oupicky D . Effect of cell membrane thiols and reduction-triggered disassembly on transfection activity of bioreducible polyplexes. Eur J Pharm Sci. 2012; 46(3):173-80. PMC: 3730823. DOI: 10.1016/j.ejps.2012.02.020. View

17.

Fuller J, Zugates G, Ferreira L, Ow H, Nguyen N, Wiesner U . Intracellular delivery of core-shell fluorescent silica nanoparticles. Biomaterials. 2007; 29(10):1526-32. DOI: 10.1016/j.biomaterials.2007.11.025. View

18.

Cohen S, Coue G, Beno D, Korenstein R, Engbersen J . Bioreducible poly(amidoamine)s as carriers for intracellular protein delivery to intestinal cells. Biomaterials. 2011; 33(2):614-23. DOI: 10.1016/j.biomaterials.2011.09.085. View

19.

Qiu K, Yu B, Huang H, Zhang P, Huang J, Zou S . A dendritic nano-sized hexanuclear ruthenium(II) complex as a one- and two-photon luminescent tracking non-viral gene vector. Sci Rep. 2015; 5:10707. PMC: 4505312. DOI: 10.1038/srep10707. View

20.

Lin C, Blaauboer C, Timoneda M, Lok M, van Steenbergen M, Hennink W . Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery. J Control Release. 2007; 126(2):166-74. DOI: 10.1016/j.jconrel.2007.11.012. View