Synthesis of Linear Polyamines with Different Amine Spacings and their Ability to Form dsDNA/siRNA Complexes Suitable for Transfection

Abstract

In this paper we report on the synthesis of diversified linear polyamine architectures with different chain lengths and compositions and their interaction with phosphate groups of DNA/siRNA. The polyplex formation between model nucleotide (dsDNA) and these linear polyamines has been determined at different nitrogen to phosphorus (N/P) ratios using small-angle neutron scattering (SANS) and atomic force microscopy (AFM) techniques. AFM images showed that while linear poly(ethylene imine) (PEI)/DNA complex results in bigger spherical aggregates, poly(propylene imine)s forms torroid and cigar shaped structures upon complexation with DNA. The poly(butylene imine)s (LPBI)s form compact and soluble DNA complexes with a radii range of R(g) = 15-30 nm. Among the studied linear polyamines, the LPBIs did show the best transfection efficiency.

Hyperbranched Polyamines for Transfection

“…From the structural point of view, polyamines used for gene transfection vary widely in their structures, which range between linear [24,[29][30][31][32][33][34][35], branched [12,30,32], hyperbranched, and perfect branched dendrimers [36]. In this chapter we present a general overview of the research reported so far using dendritic polyamines in gene delivery applications.…”

“…By using carbonyldiimidazole chemistry the terminal hydroxyl (-OH) groups from Boltorn were esterified with increasing equivalents (9,19,35,48, and 60) of diethylaminopropylamine (DEAPA) (Scheme 6). These polymers, which only contain ester bonds and terminal carbamate linkages, showed degradability, very low toxicity, and an ability to transfect cells.…”

siRNA transfection by dendritic core–shell nanocarriers

“…[26,[155][156][157][158][159][160][161][162][163] Furthermore, they can be easily modified with substitutions or additions of functional groups or by cell-or tissue-specific targeting moieties and are completely soluble in water. [164] For efficient complexation of 1 Introduction nucleic acids via electrostatic interaction, cationic polymers are used that acquire their charge from primary, secondary, tertiary, and/or quaternary amino groups.…”

“…Synthesis and structure of PEI (a) synthesis of linear PEI [161] and (b) synthesis of hyperbranched PEI [2] via acid catalyzed, ring-opening polymerization of aziridine. Each color represents a different branching unit: blue for linear units (L), black for dendritic units (D), red for terminal units (T).…”

“…[285] In the past decade several approaches to deliver DNA/ siRNA into the cell have been developed. [1,16,24,64,161,169,[286][287][288] In general, effective carriers systems require the ability to compact the nucleic acid into particles of virus-like dimensions for cellular internalization, the protection from both extracellular and intracellular nuclease degradation, and finally the intracellular controlled release of the siRNA or DNA-complex. [113] The colloidal surface and the physicochemical characteristics of DNA/siRNA polyplexes, such as size, charge, hydrophobicity, and buffering capacity, are responsible for controlling the extent and rate of delivery of genes to cells, [289] whereas the efficient release of the gene depends on the characteristics of the transfection vehicles itself.…”