Design of polymers for siRNA delivery: Recent progress and challenges

Abstract

RNA interference with the ability to specifically silence target genes has shown great potential to treat various diseases. The primary challenge for RNA interference is to effectively and selectively deliver genetic materials such as small interfering RNA (siRNA) to targeted tissues and cells in vivo. Numerous efforts have been made to overcome the extracellular and intracellular barriers during siRNA delivery. In this review, we focused on most recent advances in the design of functional polymers to achieve efficient siRNA delivery via addressing the various parameters, including siRNA binding, serum stability, specific targeting, tissue penetration, cellular internalization, endosomal escape, and intracellular siRNA release. The beneficial roles of assembled polymer nanostructures and polymerbased hybrid nanocomposites in siRNA delivery were also reviewed. Finally, the challenges and perspectives in the future development of polymer-based siRNA delivery systems will be discussed.

Polycatechols with Robust Efficiency in Cytosolic Peptide Delivery via Catechol-Boronate Chemistry

“…In order to achieve robust cytosolic peptide delivery, the polymer carriers should have a strong binding affinity with different kinds of peptides . Our previous work showed that polycatechols possess high capabilities in biomolecule binding, cell permeability, and endosome escape and thus effectively deliver siRNA and proteins inside cells. − Moreover, catechol moieties could act as a bridging ligand to bind boronic acid-rich molecules via dynamic covalent chemistry. , Here, we synthesized a class of polycatechols for cytosolic delivery of cargo peptides bearing boronate moieties to build a polypeptide-based delivery system. The polycatechols with the highest cell internalization and moderate cytotoxicity were first screened for the purpose.…”

Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p65 siRNA

“…This method of gene silencing has become a new trend in anti-cancer therapy and anti-inflammatory therapy. The main hurdles in the development of therapeutics based on siRNA are poor stability, the low efficiency of siRNA delivery to target cells, and the degradation of siRNA by nucleases in biological fluids [28]. For example, Alexander et al optimized PEI-based nanoparticles for siRNA delivery, then analyzed the results in in vitro and in vivo tumor tissue slice culture models [29].…”

Biotechnological Evolution of siRNA Molecules: From Bench Tool to the Refined Drug

“…Lipid-based nanoparticles and exosomes are, perhaps, two of the most promising vectorization strategies for gene delivery, reflected by the number of proposed clinical trials using these nanovectors for cancer [ 16 ]. With respect to polymeric particles, we can highlight the nanoparticles based on cationic polymers, which are composed of amines that can be protonated and therefore interact with siRNAs and condense them to form polyplexes [ 17 ].…”