scholarly journals Dopamine-Grafted Hyaluronic Acid Coated Hyperbranched Poly(β-Amino Esters)/DNA Nano-Complexes for Enhanced Gene Delivery and Biosafety

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 347
Author(s):  
Man Guo ◽  
Yingcai Meng ◽  
Xiaoqun Qin ◽  
Wenhu Zhou
Keyword(s):  
Hyaluronic Acid ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Genetic Diseases ◽  
Great Promise ◽  
Cationic Polymers ◽  
Nano Structure ◽  
Robust Solution ◽  
Amino Esters

Gene therapy has attracted particular attention for the treatment of various genetic diseases, and the development of gene delivery vectors is of utmost importance for in vivo applications of gene drugs. Various cationic polymers with high nucleic acid loading and intracellular transfection efficiency have been reported, however, their biological applications are limited by potential toxicity. Surface modification is a robust solution to detoxify the cationic vectors, but this can inevitably weaken the transfection efficiency. To address this dilemma, we reported the ability of a dopamine (DA)-grafted hyaluronic acid (HA) to modify gene vectors for enhanced gene delivery and biosafety. The nano-vector was formed by using branched poly(β-amino esters) (PAEs), and surface coating with HA-DA to form a core-shell nano-structure via electrostatic attraction. Upon HA-DA modification, the biosafety of the gene delivery vehicle was improved, as demonstrated by the cell cytotoxicity assay and hemolysis test. Notably, the nano-system displayed a DA-dependent transfection efficiency, in which a higher DA grafting degree resulted in better efficacy. This can be explained by the adhesive nature of DA, facilitating cell membrane interaction, as well as DA receptor mediated active targeting. At the optimal DA grafting ratio, the nano-system achieved a transfection efficiency even better than that of commonly used polyethylenimine (PEI) vectors. Together with its excellent biocompatibility, the vector presented here holds great promise for gene delivery applications.

scholarly journals Chondroitin Sulfate Capsule System for Efficient and Secure Gene Delivery

2010 ◽  
Vol 13 (3) ◽  
pp. 351 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Shintaro Fumoto ◽  
Koyo Nishida ◽  
Kayo Yamamoto ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Chondroitin Sulfate ◽  
Transfection Efficiency ◽  
Animal Experiments ◽  
Ternary Complexes ◽  
Trimethylammonium Chloride ◽  
Cationic Polymers ◽  
Low Cytotoxicity

Purpose. In this study, we developed various ternary complexes of encapsulated polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their universal usefulness for gene delivery. Methods. To prepare the cationic complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine, poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE) liposomes. CS was added to the cationic complexes for constructions of ternary complexes. We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of the ternary complexes. Result. The cationic polymers and cationic liposomes bound to pDNA and formed stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes showed high transgene efficiency in B16-F10 cells; however, they also had high cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the polyplexes and lipoplexes and form stable anionic particles without disrupting their structures. The ternary complexes encapsulated by CS showed high transgene efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the result of animal experiments, the polyplexes had little transgene efficiency after intravenous administration in mice, whereas polyplexes encapsulated by CS showed specifically high transgene efficiency in the spleen. The capsulation of CS, however, reduced the high transgene efficiency of the lipoplexes. Conclusion. These results indicate that CS can contribute to polyplex-mediated gene delivery systems for effective and safe gene therapy.

Hyaluronic acid–PEI–cyclodextrin polyplexes: implications for in vitro and in vivo transfection efficiency and toxicity

RSC Advances ◽  
2015 ◽  
Vol 5 (51) ◽  
pp. 41144-41154 ◽  
Author(s):  
S. Jain ◽  
S. Kumar ◽  
A. K. Agrawal ◽  
K. Thanki ◽  
U. C. Banerjee
Keyword(s):  
Hyaluronic Acid ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
In Vivo Transfection

The present study reveals novel HA–PEI–CyD polyplexes as non-viral vectors for gene delivery.

scholarly journals The transition from linear to highly branched poly(β-amino ester)s: Branching matters for gene delivery

2016 ◽  
Vol 2 (6) ◽  
pp. e1600102 ◽  
Author(s):  
Dezhong Zhou ◽  
Lara Cutlar ◽  
Yongsheng Gao ◽  
Wei Wang ◽  
Jonathan O’Keeffe-Ahern ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Branched Polymers ◽  
Nonviral Gene Delivery ◽  
Great Promise ◽  
Amino Ester ◽  
Design And Synthesis ◽  
Gene Delivery Vectors

Nonviral gene therapy holds great promise but has not delivered treatments for clinical application to date. Lack of safe and efficient gene delivery vectors is the major hurdle. Among nonviral gene delivery vectors, poly(β-amino ester)s are one of the most versatile candidates because of their wide monomer availability, high polymer flexibility, and superior gene transfection performance both in vitro and in vivo. However, to date, all research has been focused on vectors with a linear structure. A well-accepted view is that dendritic or branched polymers have greater potential as gene delivery vectors because of their three-dimensional structure and multiple terminal groups. Nevertheless, to date, the synthesis of dendritic or branched polymers has been proven to be a well-known challenge. We report the design and synthesis of highly branched poly(β-amino ester)s (HPAEs) via a one-pot “A2 + B3 + C2”–type Michael addition approach and evaluate their potential as gene delivery vectors. We find that the branched structure can significantly enhance the transfection efficiency of poly(β-amino ester)s: Up to an 8521-fold enhancement in transfection efficiency was observed across 12 cell types ranging from cell lines, primary cells, to stem cells, over their corresponding linear poly(β-amino ester)s (LPAEs) and the commercial transfection reagents polyethyleneimine, SuperFect, and Lipofectamine 2000. Moreover, we further demonstrate that HPAEs can correct genetic defects in vivo using a recessive dystrophic epidermolysis bullosa graft mouse model. Our findings prove that the A2 + B3 + C2 approach is highly generalizable and flexible for the design and synthesis of HPAEs, which cannot be achieved by the conventional polymerization approach; HPAEs are more efficient vectors in gene transfection than the corresponding LPAEs. This provides valuable insight into the development and applications of nonviral gene delivery and demonstrates great prospect for their translation to a clinical environment.

scholarly journals Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Qiu-Lan Zhou ◽  
Zhi-Yi Chen ◽  
Yi-Xiang Wang ◽  
Feng Yang ◽  
Yan Lin ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Research Progress ◽  
Great Promise ◽  
Blood Capillary ◽  
Tumor Tissues ◽  
Ultrasound Molecular Imaging ◽  
Pass Through ◽  
Capillary Walls

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

scholarly journals A ligand-based system for receptor-specific delivery of proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariano Maffei ◽  
Chiara Morelli ◽  
Ellie Graham ◽  
Stefano Patriarca ◽  
Laura Donzelli ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Protein Delivery ◽  
Genetic Diseases ◽  
Cell Surface Receptor ◽  
Viral Gene ◽  
Promising Alternative ◽  
Large Proteins ◽  
Reporter Mice ◽  
Surface Receptor

AbstractGene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand’s cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

scholarly journals Ultrasound-Mediated Gene Delivery with Cationic Versus Neutral Microbubbles: Effect of DNA and Microbubble Dose on In Vivo Transfection Efficiency

Theranostics ◽  
2012 ◽  
Vol 2 (11) ◽  
pp. 1078-1091 ◽  
Author(s):  
Cedric M. Panje ◽  
David S. Wang ◽  
Marybeth A. Pysz ◽  
Ramasamy Paulmurugan ◽  
Ying Ren ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
In Vivo Transfection

scholarly journals Exploitation of De Novo Helper-Lipids for Effective Gene Delivery.

2009 ◽  
Vol 11 (4) ◽  
pp. 56 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Mugen Teshima ◽  
Koyo Nishida ◽  
Junzo Nakamura ◽  
...  
Keyword(s):  
Gene Delivery ◽  
De Novo ◽  
Transfection Efficiency ◽  
The Other ◽  
Penetration Enhancers ◽  
Cell Toxicity ◽  
In Vivo Transfection ◽  
In Vitro Transfection

Purpose: In gene delivery, a fusogenic lipid such as dioleyl phosphatidylethanolamine (DOPE) which is a component of cationic liposomal vector is important factor for effective transfection efficiency. We investigated the effect of penetration enhancers as alternative helper-lipids to DOPE. Methods: Transdermal penetraion enhancers such as N-lauroylsarcosine (LS), (R)-(+)-limonene (LM), vitamin E (VE), and phosphatidyl choline from eggs (EggPC) were used in this experiments as helper-lipids with N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethlylammonium chloride (DOTMA) and cholesterol (CHOL). We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of plasmid DNA/cationic liposomes complexes. Results: In transfection experiments in vitro, the cationic lipoplexes containing LS had highest transfection efficiency among the other lipoplexes independently of FBS. Furthermore, the lipoplexes containing LS had lowest cell toxicity among the other lipoplexes in the presence of FBS. As the results of erythrocytes interaction experiment, DOTMA/LS/CHOL, DOTMA/VE/CHOL, and DOTMA/EggPC/CHOL lipoplexes showed extremely lower hematotoxicity. On the basis of these results, the in vivo transfection efficiencies of the lipoplexes were examined. The lipoplexes containing LS had the highest transfection activity among the other lipoplexes. Conclusion: In conclusion, several transdermal penetration enhancers are available for alternative helper-lipids to DOPE in cationic liposomal vectors. Among them, DOTMA/LS/CHOL lipoplexes showed superior characteristics in in vitro transfection efficiency, cell toxicity, hematotoxicity, and in vivo transfection efficiency.

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