A dendritic catiomer with an MOF motif for the construction of safe and efficient gene delivery systems

2017 ◽  
Vol 5 (42) ◽  
pp. 8322-8329 ◽  
Author(s):  
Shuqi Dong ◽  
Qixian Chen ◽  
Wei Li ◽  
Zhu Jiang ◽  
Jianbiao Ma ◽  
...  

The dendritic catiomer using biocompatible Zr-MOFs as the core exhibited a markedly higher transfection efficiency and lower cytotoxicity than the commercial gold standard branched PEI25k in A549 cells.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.


2021 ◽  
Author(s):  
Tahereh Kashkoulinejad-Kouhi ◽  
Shadi Sawalha ◽  
Shahrokh Safarian ◽  
Blanca Arnaiz

Aim: Several types of nanocarriers, most of which show significant cytotoxicity, have been developed to overcome the problem of gene-delivery barriers. Biocompatibility, low toxicity and water solubility of carbon nanodots (CNDs) are major advantages that recommend them as delivery systems. Materials & methods: We present a simple method to produce positively charged CNDs. Ethanolamine, ethylenediamine and hydrogen peroxide were utilized to synthesize these CNDs. Results & conclusion: Our results indicated that delivery of the CND–siGFP complex led to significant switching-off of the fluorescence of the GFP-expressing A549 cell. Next, the A549 cells were transfected with siRNA against BiP, which is a pivotal protein in the chemotherapy resistance of cancer cells. The expression levels of BiP decreased remarkably.


2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng

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.


Nano LIFE ◽  
2010 ◽  
Vol 01 (03n04) ◽  
pp. 219-237 ◽  
Author(s):  
SHARDOOL JAIN ◽  
HUSAIN ATTARWALA ◽  
MANSOOR AMIJI

Gene therapy holds tremendous promise in prevention and treatment of diseases as the approach is based on regulating the expression of genes that are responsible for pathological conditions. The biggest bottleneck for gene delivery has been the development of safe and efficacious delivery systems. Although non-viral vectors are considered as much safer options than their viral counterparts, they suffer from low transfection efficiency. In this review, we highlight the role of non-condensing polymeric delivery systems for oral and systemic gene delivery. Using evidence from contemporary literature, non-condensing polymeric microparticle and nanoparticle systems afford physical encapsulation of the nucleic acid construct and can be engineered for targeted delivery to tissues and cells. Additionally, these systems have shown less toxicity and afford sustained cytoplasmic DNA delivery for efficient nuclear uptake and transfection for both DNA vaccines and therapeutic genes.


2008 ◽  
pp. 2001 ◽  
Author(s):  
Alejandro Díaz-Moscoso ◽  
Patricia Balbuena ◽  
Marta Gómez-García ◽  
Carmen Ortiz Mellet ◽  
Juan M. Benito ◽  
...  

2007 ◽  
Vol 130 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Jiji Chen ◽  
Buning Tian ◽  
Xiang Yin ◽  
Yanqiong Zhang ◽  
Duosha Hu ◽  
...  

2015 ◽  
Vol 3 (6) ◽  
pp. 1068-1078 ◽  
Author(s):  
Liang Luan ◽  
Qingbin Meng ◽  
Liang Xu ◽  
Zhao Meng ◽  
Husheng Yan ◽  
...  

A series of peptides containing multiple functional fragments were designed as gene-delivery vectors with transfection efficiency comparable to Lipofectamine 2000.


2021 ◽  
Vol 22 (16) ◽  
pp. 8537
Author(s):  
Sofía Mirón-Barroso ◽  
Elena B. Domènech ◽  
Sonia Trigueros

Nanomaterials are currently being developed for the specific cell/tissue/organ delivery of genetic material. Nanomaterials are considered as non-viral vectors for gene therapy use. However, there are several requirements for developing a device small enough to become an efficient gene-delivery tool. Considering that the non-viral vectors tested so far show very low efficiency of gene delivery, there is a need to develop nanotechnology-based strategies to overcome current barriers in gene delivery. Selected nanostructures can incorporate several genetic materials, such as plasmid DNA, mRNA, and siRNA. In the field of nanotechnologies, there are still some limitations yet to be resolved for their use as gene delivery systems, such as potential toxicity and low transfection efficiency. Undeniably, novel properties at the nanoscale are essential to overcome these limitations. In this paper, we will explore the latest advances in nanotechnology in the gene delivery field.


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