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A nucleus penetrating vehicle is indispensible when seeking to deliver plasmid DNA for gene transfection. In this study, dendrimers with terminal thymine groups were synthesized to meet this objective. Through modifications of the hydrophilic and neutral thymine moieties on hyperbranched peripheries, these dendrimers can achieve biosafety, efficient endosomal escape ability, cytosolic accessibility, and eventually, nuclear entry for the purposes of gene transfection. After optimization of the thymine coverages, better gene expression can only be achieved while replacing ∼50% of the amine groups of a dendrimer with thymine moieties. Presumably, a specific dendrimer comprising thymine and primary amines might possess a synergistic effect to promote pDNA condensation via the cooperation of electrostatic interaction and hydrogen bonding. In comparison, a dendrimer entirely capped by thymine can lose external amines, decreasing pDNA complexity and stability, which would cause poor gene transfection. The utility of specific thymine-capped dendrimers in vivo level was demonstrated to successfully and efficiently deliver plasmid DNA at a low complex ratio into mouse muscle by intramuscular injection. Upon the easy accessibility of intramuscular administration, the capability of thymine-capped dendrimers might be potentially used in immunotherapeutic gene transfection in the future. [ABSTRACT FROM AUTHOR]

RNAi-mediated gene silencing has great potential for treating various diseases, including cancer, by delivering a specific short interfering RNA (siRNA) to knock down pathogenic mRNAs and suppress protein translation. Although many researchers are dedicated to devising polymer-based vehicles for exogenous in vitro siRNA transfection, few synthetic vehicles are feasible in vivo. Recent studies have presented copolymer-based vectors that are minimally immunogenic and facilitate highly efficient internalizing of exogenous siRNA, compared with homopolymer-based vectors. Cationic segments, organelle-escape units, and degradable fragments are essential to a copolymer-based vehicle for siRNA delivery. The majority of these cationic segments are derived from polyamines, including polylysine, polyarginine, chitosan, polyethylenimines and polyamidoamine dendrimers. Not only do these cationic polyamines protect siRNA, they can also promote disruption of endosomal membranes. Degradable fragments of copolymers must be derived from various polyelectrolytes to release the siRNA once the complexes enter the cytoplasm. This review describes recent progress in copolymer-mediated siRNA delivery, including various building blocks for biocompatible copolymers for efficient in vitro siRNA delivery, and a useful basis for addressing the challenges of in vivo siRNA delivery. [ABSTRACT FROM AUTHOR]