Functional Polymers for Targeted Delivery of Nucleic Acid Drugs

Abstract

Cationic polymers have been chemically modified with a variety of targeting molecules such as peptides, proteins, antibodies, sugars and vitamins for targeted delivery of nucleic acid drugs to specific cells. Stimuli-sensitive polymers exhibiting different size, charge and conformation in response to physiological signals from specific cells have also been utilized for targeted delivery. To achieve target-specific delivery of nucleic acids, conjugation chemistry is critical to produce stable nanosized polyplexes tethered with cell-recognizable ligands for facile cellular uptake via a receptor-mediated endocytic pathway. In this review, synthetic strategies of functional cationic polymers with various targeting ligands are presented.

Self-Assembled and Nanostructured siRNA Delivery Systems

“…Thus, a large number of targeting moieties, such as growth factors, antibodies, sugar molecules and peptides, have been widely investigated to develop tissue-or cell-specific delivery systems for drugs, genes, and diagnostic imaging agents (73,93). Although PEGylation is considered an attractive strategy for the stabilization and prolonged circulation of nanoparticles, PEGylation frequently reduces the cellular uptake of PEGylated nanoparticles by the steric hindrance effect, which is the same phenomenon observed in the decreased adsorption of blood components (94).…”

“…Despite the high transfection efficiency, the major drawbacks of PEI as a gene carrier are high cytotoxicity and non-degradability. Although acute cell cytotoxicity of PEI caused by direct interactions with the plasma membrane may be reduced to some extent by the charge-shielding effect of the PEG layer, high molecular weight PEI (25 kDa) still has the potential to elicit long-term toxicity since it is hardly degradable in a physiological environment (6,73). PLL, which has been used for transfection due to its excellent DNA compaction ability, was utilized as a condensing agent for the formation of polyplex micelles with siRNA-PEG conjugates (47).…”

Localized Delivery of Antisense Oligonucleotides by Cationic Hydrogel Suppresses TNF-α Expression and Endotoxin-Induced Osteolysis

“…Nanoparticle-based delivery systems encountered great obstacles when used in vivo because of poor targeting effects (5)(6)(7). Attempts using ligand modification to improve the targeting delivery ability of nanoparticles only achieved some uncertain results in most cases (8,9).…”

Self-crosslinked polyethylenimine nanogels for enhanced intracellular delivery of siRNA

“…The formation of polyelectrolyte complex between siRNA and PEI effectively provide siRNA protection from enzymatic degradation and enhanced intracellular uptake via endocytosis. [8][9][10][11][12] Branched PEI (bPEI) has primary, secondary, and tertiary amine groups with different pKa values, in which only one third of amine groups are protonated in a physiological pH. The unprotonated amine groups can absorb protons when the polymer is located in an acidic environment.…”