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Polymers Used for the Delivery of Genes in Gene Therapy
Published in Ijeoma F. Uchegbu, Andreas G. Schätzlein, Polymers in Drug Delivery, 2006
Pei Lee Kan, Andreas G. Schätzlein, Ijeoma F. Uchegbu
Polymeric gene delivery systems (cationic) are usually positively charged at physiological pH [8], and the most commonly used polymers are shown in Figure 12.1. Cationic polymers, by virtue of their possession of protonable groups at physiological pH (amine groups), are able to undergo electrostatic interactions with DNA, the latter of which is anionic at physiological pH [8]. DNA is compacted within the electrostatic complex, a process termed DNA condensation, and the colloidal particles that result from this process are known as polyplexes (Figure 12.2). It is these polyplexes that enable the transport of DNA across the various biological barriers to its nuclear destination.
DNA—Surfactant Systems
Published in Victor M. Starov, Nanoscience, 2010
Rita Dias, Carmen Morán, Diana Costa, Maria Miguel, Björn Lindman
The interest in DNA–cosolute interactions and DNA condensation is growing rapidly (for a recent review, see Dias and Lindman, in press). DNA condensation or compaction can be induced by a variety of processes and agents such as multivalent ions, solvents with low dielectric constants, cationic surfactants, and polymers and even high concentrations of neutral polymers and surfactants.
The emergence of nanoporous materials in lung cancer therapy
Published in Science and Technology of Advanced Materials, 2022
Deepika Radhakrishnan, Shan Mohanan, Goeun Choi, Jin-Ho Choy, Steffi Tiburcius, Hoang Trung Trinh, Shankar Bolan, Nikki Verrills, Pradeep Tanwar, Ajay Karakoti, Ajayan Vinu
CSN has also been used for the delivery of genetic materials. Researchers have modified CSN with the positively charged proteins for attracting DNAs. An advantage of such a strategy is that it can enhance the total DNA condensation and nuclear localisation in cancer cells. To achieve a targeted therapy, Rong et al. designed a gene delivery platform synergising BTZ with histone H2A-hybrid cationic peptide along with upconversion guided mesoporous CSN. The drug was loaded in the mesopores and the gene p53 peptides/H2A was functionalised on the surface of MSNs. In this case, the core contains upconverter photoluminescent particles coated with a shell of CTAB, and the H2A were functionalised by EDC/NHS-mediated grafting reaction [198]. These materials could achieve a higher 4.17 fold increase of the relative transcriptional level of p53, which is confirmed with the qRT-PCR assay. Thus, a synergetic effect of transfection of p53 gene to the p53 null NCI-H1299 cells with the drug BTZ could be achieved and initiated apoptosis of the mitochondria-mediated pathways. This is an initial study to initiate strategies for delivering the genes to any cells/tumours.
Preparation and characterization of polyamidoamine dendrimers conjugated with cholesteryl-dipeptide as gene carriers in HeLa cells
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Le Thi Thuy, Minyoung Choi, Minhyung Lee, Joon Sig Choi
The DNA condensation ability of polymers is essential for efficient gene delivery. We performed agarose gel electrophoresis of polyplexes obtained at different weight ratios (Figure 4) to evaluate the formation of the polymer/DNA complexes. Lanes 1 and 2 were loaded with DNA only (negative control) and PEI 25 kDa polyplexes (w/w = 2) (positive control), respectively. Lanes 3, 4, and 5 were loaded with weight ratios of PAMAM G2/pDNA = 4, 8, and 16, respectively. Lanes 6, 7, 8, and 9 were loaded with weight ratios of PAMAM G2-HR/pDNA = 4, 8, 16, and 24, respectively. Lanes 10, 11, 12, and 13 were loaded with weight ratios of PAMAM G2-HRChol 6%/pDNA = 4, 8, 16, and 24, respectively. Lanes 14, 15, 16, and 17 were loaded with weight ratios of PAMAM G2-HRChol 23%/pDNA = 4, 8, 16, and 24, respectively. PEI 25 kDa was completely retarded by DNA at a weight ratio of 2. In contrast, the complete retardation of PAMAM G2 was observed at a weight ratio of 8. The amine groups contribute to the electrostatic interactions between the polymer and DNA. Therefore, PEI 25 kDa is better than the PAMAM G2 dendrimer in terms of complex formation. A previous study indicated that the guanidine group from arginine can easily adhere to DNA and cell membranes [33, 34]. Similar to these findings, our data suggest that the modified arginine content on the PAMAM G2 dendrimer surface improved DNA condensation. Complete retardation of PAMAM G2-HR, PAMAM G2-HRChol 6%, and PAMAM G2-HRCHol 23% dendrimers was observed at a weight ratio of 4, whereas native PAMAM G2 dendrimers were unable to condense with DNA at this ratio. These results indicate that the PAMAM G2 dendrimer derivatives are promising for gene delivery.