Exploring Advantages/disadvantages and Improvements in Overcoming Gene Delivery Barriers of Amino Acid Modified Trimethylated Chitosan

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2014 Dec 24

PMID 25534683

Citations 6

Authors

Hao Zheng

Cui Tang

Chunhua Yin

Affiliations

Soon will be listed here.

Abstract

Purpose: Present study aimed at exploring advantages/disadvantages of amino acid modified trimethylated chitosan in conquering multiple gene delivery obstacles and thus providing comprehensive understandings for improved transfection efficiency.

Methods: Arginine, cysteine, and histidine modified trimethyl chitosan were synthesized and employed to self-assemble with plasmid DNA (pDNA) to form nanocomplexes, namely TRNC, TCNC, and THNC, respectively. They were assessed by structural stability, cellular uptake, endosomal escape, release behavior, nuclear localization, and in vitro and in vivo transfection efficiencies. Besides, sodium tripolyphosphate (TPP) was added into TRNC to compromise certain disadvantageous attributes for pDNA delivery.

Results: Optimal endosomal escape ability failed to bring in satisfactory transfection efficiency of THNC due to drawbacks in structural stability, cellular uptake, pDNA liberation, and nuclear distribution. TCNC evoked the most potent gene expression owing to multiple advantages including sufficient stability, preferable uptake, efficient pDNA release, and high nucleic accumulation. Undesirable stability and insufficient pDNA release adversely affected TRNC-mediated gene transfer. However, incorporation of TPP could improve such disadvantages and consequently resulted in enhanced transfection efficiencies.

Conclusions: Coordination of multiple contributing effects to conquer all delivery obstacles was necessitated for improved transfection efficiency, which would provide insights into rational design of gene delivery vehicles.

Citing Articles

The Multifaceted Histidine-Based Carriers for Nucleic Acid Delivery: Advances and Challenges.

He J, Xu S, Mixson A Pharmaceutics. 2020; 12(8).

PMID: 32823960 PMC: 7465012. DOI: 10.3390/pharmaceutics12080774.

Biodegradable Polymers for Gene Delivery.

Thomas T, Tajmir-Riahi H, Pillai C Molecules. 2019; 24(20).

PMID: 31627389 PMC: 6832905. DOI: 10.3390/molecules24203744.

Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery.

Yasar H, Ho D, De Rossi C, Herrmann J, Gordon S, Loretz B Polymers (Basel). 2019; 10(3).

PMID: 30966288 PMC: 6415184. DOI: 10.3390/polym10030252.

Delivery of expression constructs of secreted frizzled-related protein 4 and its domains by chitosan-dextran sulfate nanoparticles enhances their expression and anti-cancer effects.

Perumal V, Arfuso F, Chen Y, Fox S, Dharmarajan A Mol Cell Biochem. 2017; 443(1-2):205-213.

PMID: 29185158 DOI: 10.1007/s11010-017-3225-4.

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy.

Babu A, Ramesh R Mar Drugs. 2017; 15(4).

PMID: 28346381 PMC: 5408242. DOI: 10.3390/md15040096.

References

Ding J, He R, Zhou G, Tang C, Yin C . Multilayered mucoadhesive hydrogel films based on thiolated hyaluronic acid and polyvinylalcohol for insulin delivery. Acta Biomater. 2012; 8(10):3643-51. DOI: 10.1016/j.actbio.2012.06.027. View

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

Schmitz T, Bravo-Osuna I, Vauthier C, Ponchel G, Loretz B, Bernkop-Schnurch A . Development and in vitro evaluation of a thiomer-based nanoparticulate gene delivery system. Biomaterials. 2006; 28(3):524-31. DOI: 10.1016/j.biomaterials.2006.08.017. View

Zhao X, Yin L, Ding J, Tang C, Gu S, Yin C . Thiolated trimethyl chitosan nanocomplexes as gene carriers with high in vitro and in vivo transfection efficiency. J Control Release. 2010; 144(1):46-54. DOI: 10.1016/j.jconrel.2010.01.022. View

Zheng H, Tang C, Yin C . The effect of crosslinking agents on the transfection efficiency, cellular and intracellular processing of DNA/polymer nanocomplexes. Biomaterials. 2013; 34(13):3479-88. DOI: 10.1016/j.biomaterials.2013.01.072. View

Bayer N, Schober D, Prchla E, Murphy R, Blaas D, Fuchs R . Effect of bafilomycin A1 and nocodazole on endocytic transport in HeLa cells: implications for viral uncoating and infection. J Virol. 1998; 72(12):9645-55. PMC: 110474. DOI: 10.1128/JVI.72.12.9645-9655.1998. View

Gu J, Wang X, Jiang X, Chen Y, Chen L, Fang X . Self-assembled carboxymethyl poly (L-histidine) coated poly (β-amino ester)/DNA complexes for gene transfection. Biomaterials. 2011; 33(2):644-58. DOI: 10.1016/j.biomaterials.2011.09.076. View

Han L, Tang C, Yin C . Effect of binding affinity for siRNA on the in vivo antitumor efficacy of polyplexes. Biomaterials. 2013; 34(21):5317-27. DOI: 10.1016/j.biomaterials.2013.03.060. View

Gilleron J, Querbes W, Zeigerer A, Borodovsky A, Marsico G, Schubert U . Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat Biotechnol. 2013; 31(7):638-46. DOI: 10.1038/nbt.2612. View

10.

Peng Q, Zhong Z, Zhuo R . Disulfide cross-linked polyethylenimines (PEI) prepared via thiolation of low molecular weight PEI as highly efficient gene vectors. Bioconjug Chem. 2008; 19(2):499-506. DOI: 10.1021/bc7003236. View

11.

Thanou M, Kotze A, Scharringhausen T, Luessen H, De Boer A, Verhoef J . Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal caco-2 cell monolayers. J Control Release. 2000; 64(1-3):15-25. DOI: 10.1016/s0168-3659(99)00131-5. View

12.

Azari F, Sandros M, Tabrizian M . Self-assembled multifunctional nanoplexes for gene inhibitory therapy. Nanomedicine (Lond). 2011; 6(4):669-80. DOI: 10.2217/nnm.11.23. View

13.

Layek B, Singh J . Amino acid grafted chitosan for high performance gene delivery: comparison of amino acid hydrophobicity on vector and polyplex characteristics. Biomacromolecules. 2013; 14(2):485-94. DOI: 10.1021/bm301720g. View

14.

He C, Yin L, Tang C, Yin C . Multifunctional polymeric nanoparticles for oral delivery of TNF-α siRNA to macrophages. Biomaterials. 2013; 34(11):2843-54. DOI: 10.1016/j.biomaterials.2013.01.033. View

15.

Gabrielson N, Lu H, Yin L, Li D, Wang F, Cheng J . Reactive and bioactive cationic α-helical polypeptide template for nonviral gene delivery. Angew Chem Int Ed Engl. 2011; 51(5):1143-7. PMC: 3555134. DOI: 10.1002/anie.201104262. View

16.

Casettari L, Vllasaliu D, Lam J, Soliman M, Illum L . Biomedical applications of amino acid-modified chitosans: a review. Biomaterials. 2012; 33(30):7565-83. DOI: 10.1016/j.biomaterials.2012.06.104. View

17.

Shigeta K, Kawakami S, Higuchi Y, Okuda T, Yagi H, Yamashita F . Novel histidine-conjugated galactosylated cationic liposomes for efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells. J Control Release. 2007; 118(2):262-70. DOI: 10.1016/j.jconrel.2006.12.019. View

18.

Chang K, Higuchi Y, Kawakami S, Yamashita F, Hashida M . Development of lysine-histidine dendron modified chitosan for improving transfection efficiency in HEK293 cells. J Control Release. 2011; 156(2):195-202. DOI: 10.1016/j.jconrel.2011.07.021. View

19.

Khalil I, Kogure K, Futaki S, Harashima H . Octaarginine-modified liposomes: enhanced cellular uptake and controlled intracellular trafficking. Int J Pharm. 2008; 354(1-2):39-48. DOI: 10.1016/j.ijpharm.2007.12.003. View

20.

Lee D, Zhang W, Shirley S, Kong X, Hellermann G, Lockey R . Thiolated chitosan/DNA nanocomplexes exhibit enhanced and sustained gene delivery. Pharm Res. 2006; 24(1):157-67. DOI: 10.1007/s11095-006-9136-9. View