Transfection synthetic polymers

Synthetic polymer. Among the cationic synthetic polymers used for gene delivery are polyethylenimine (PEI), polyamidoamine dendrimers, and poly(2-dimethylaminoethyl methacrylate).161-164 Depending on the flexibility (or rigidity) of the polymers, they form either a small (<100 nm) DNA polyplex or a large (>1 to 10 pm) DNA polyplex.165 More detailed physicochemical properties and their transfection efficacy are to be discussed. 

Gelatin, which is a simply denatured collagen, has shown promise in vitro and in vivo as an shRNA delivery vehicle. Cationized gelatin nanoparticles are relatively simple to produce when compared to synthetic polymers (61). They have been shown to have an in vitro transfection efficiency of approximately one order of magnitude less than PEI, but show approximately four-fold less cytotoxicity (62,63). 

Several of the most effective polymeric delivery systems were polyamidoamine den-drimers (220) and polyethyleneimines (PEI) (221). Being non-biodegradable, these synthetic polymers posed a potential toxicity to cell therefore, biodegradable polypeptides like PLL and protamine were used for condensation and delivery of gene, but they had limited efficacy in transfection (222, 223). They were usually used with cationic lipids to obtain enhanced transfection activity (178,201). Among the biodegradable polymers, chitosan... 

Dextran can be modified easily and cationic derivatives are obtained by reaction with diethylaminoethyl (DEAE) reagents or spermine. DEAE-dextran is one of the pioneer cationic polymers for gene delivery. However, PLL and other synthetic polymers have replaced dextran these days because of low transfection efficiency and toxicity problems of DEAE-dextran. Spermine-dextran (MW 9000-11 000 g mol ) is used as an siRNA delivery agent to cancer cells, with low toxicity and high loading capacity on HeLa-Zwc cells, and was proved to be a safe and effective acid-sensitive carrier for gene delivery by Cohen et al. Researchers showed that cationic dextran derivatives (MW 70 kDa) have also reverse tumor-associated macrophage (TAM) polarization, promote IL-12 expression in tumor TAMs and thereby enhance the tumoricidal capacity of TAMs. ... 

Natural polymers such as chitosan and alginate have received recent attention due to their desirable biodegradability characteristics [25-27]. Research in this field, to date limited in contrast to liposomes and synthetic polymers, indicates that these natural vectors have inferior transfection capabilities when... 

It is evident that particle-based vectors have yet to reach their envisioned capabilities. Research focus has shifted from viral vectors, which continue to offer the highest transfection efficiency, through synthetic polymer and Hposome systems, commercially available and suitable for in vitro transfection, to natural compounds in search of transfection using a biodegradable vector. The enhanced biocompatibility of peptides and natural biopolymers will certainly drive research as the quest for suitable in vivo vectors continues, though the balance between attaining biocompatibihty while preserving transfection efficiency has yet to be found. 

Alternatively to the use of hpids for the development of deUvery systems, polymeric materials can be also used as building blocks. As with Upid-based delivery systems for nucleic acids, polymers were first used in gaie deUvery as a part of the development of new DNA transfection vectors (Wu and Wu, 1987). Polymers can be synthesized in different lengths, with different geometry (linear versus branched), and with substitution or addition of functional groups. As such, there is a wide variety of natural and synthetic polymers currently used for siRNA and DNA deUvery, such as chitosan (Yao et al., 2015), polylactic-co-glycoUc acid (Lee et al., 2011), or polyethylenimine (PEI Francis et al., 2014). 

Lynn DM, Anderson DG, Putnam D, Langer R (2001) Accelerated discovery of synthetic transfection vectors parallel synthesis and screening of a degradable polymer library. J Am Chem Soc 123 8155-8156... 

Abstract In the late 1980s independent work by Feigner and Behr pioneered the use of cationic materials to complex and deliver nucleic acids into eukaryotic cells. Since this time, a vast number of synthetic transfection vectors, which are typically divided into two main transfectors , have been developed namely (1) cationic lipids and (2) polycationic polymers. In this chapter the main synthetic approaches used for the synthesis of these compounds will be reviewed with particular attention paid to cationic lipids and dendrimers. This review is aimed primarily at the younger audience of doctoral students and non-specialist readers. 

The structure of cationic lipids and polymers is readily amenable to chemical modification [35, 36] allowing the exploration of a virtually unlimited number of combinations and strategies at the mercy of chemists creative abilities. Various reviews have been focused on cationic lipids, dendrimers and polymers in terms of their chemical structures and their transfection properties [36—41], in an attempt to shed some light on the chemical requirements necessary to mediate gene delivery. The focus of this chapter will be to explore these carriers from a synthetic perspective, with a description of the chemical strategies used for the preparation via synthetic organic chemistry (excluding polymer synthesis) of cationic lipids and dendrimers. 

Abstract Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific dehvery is also briefly... 

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