Enhancing in vivo circulation and siRNA delivery with biodegradable polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) copolymers

Dual Responsive, Stabilized Nanoparticles for Efficient In Vivo Plasmid Delivery

“…[15][16][17] For example, hydrophobized PEI derivatives have improved blood circulation time and higher transfection efficacy compared to parent PEI. [18][19][20][21] Hydrophobic modification of polycations with poly(lactide) (PLA) or poly(ε-caprolactone) (PCL) reduce the cytotoxicity of polycations while promoting the overall biodegradability of gene carriers. [22][23][24][25] Another important consideration in clinical translation of non-viral vectors is the controlled synthesis of well-defined materials.…”

“…[18][19][20][21] Hydrophobic modification of polycations with poly(lactide) (PLA) or poly(ε-caprolactone) (PCL) reduce the cytotoxicity of polycations while promoting the overall biodegradability of gene carriers. [22][23][24][25] Another important consideration in clinical translation of non-viral vectors is the controlled synthesis of well-defined materials. The rapid advance in controlled radical living polymerization (CRLP), such as reversible addition-fragmentation chain transfer (RAFT) polymerization, and atom transfer radical polymerization (ATRP), has enabled the synthesis of well-defined cationic polymers with pre-selected composition and narrowly-distributed molecular weight, parameters that have been shown to affect both transfection efficiency and cytotoxicity.…”

“…[35,36] The Kissel group has demonstrated that modification of PEG-PEI with PCL results in polyplexes that are more stable in the systemic circulation. [21,22] We hypothesized that polycations hydrophobized by PCL modification via a disulfide bond might form polyplexes that have improved extracellular stability in in vivo environments but that destabilize in intracellular environments after reduction-triggered PCL release. The entrapment of OEG chains in the polyplexes has been theorized to lead to more thermodynamic destabilization compared to unmodified polycations.…”

Chitosan layered gold nanorods as synergistic therapeutics for photothermal ablation and gene silencing in triple-negative breast cancer

“…In particular, it is important that nanodelivery systems can reduce uptake by the reticuloendothelial system (RES), enhance tumor accumulation through e.g. the enhanced permeability and retention (EPR) effect, and enhance endosomal/ lysosomal escape [9][10][11][12].…”

Engineering biodegradable micelles of polyethylenimine-based amphiphilic block copolymers for efficient DNA and siRNA delivery

“…They are usually formed by self-assembly of amphiphilic block-or graft-copolymers with a typical core-shell morphology. Compared to homo-polymers like PEI, polymeric micelles might offer several unique advantageous features for nucleic acid delivery such as the capacity to condense and protect the nucleic acid segment, while showing a higher colloidal stability, longer in vivo circulation time, improved cell association and internalization, enhanced transfection efficiency as well as lower toxicity [26,28]. Importantly, their physical and biological properties can be easily tuned by using multiple copolymers with different shell-forming blocks to form co-assembled micellar structures [27,29,30].…”