Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush

Abstract

MicroRNA (miRNA) has great potential to treat a wide range of illnesses by regulating the expression of eukaryotic genes. Biomaterials with high transfection efficiency and low toxicity are needed to deliver miRNA to target cells. In this study, a biodegradable and biocompatible cationic polymer (PDAPEI) was synthetized from low molecular weight polyethyleneimine (PEI1.8kDa) cross-linked with 2,6-pyridinedicarboxaldehyde. PDAPEI showed a lower cytotoxicity and higher transfection efficiency than PEI25kDa in transfecting miR-221/222 into rat Schwann cells (SCs). The upregulation of miR-221/222 in SCs promoted the expression of nerve growth factor and myelin basic protein in vitro. The mouse sciatic nerve crush injury model was used to evaluate the effectiveness of PDAPEI/miR-221/222 complexes for nerve regeneration in vivo. The results of electrophysiological tests, functional assessments, and histological and immunohistochemistry analyses demonstrated that PDAPEI/miR-221/222 complexes significantly promoted nerve regeneration after sciatic nerve crush, specifically enhancing remyelination. All these results show that the use of PDAPEI to deliver miR-221/222 may provide a safe therapeutic means of treating nerve crush injury and may help to overcome the barrier of biomaterial toxicity and low efficiency often encountered during medical intervention.

miRNA-205 Nanoformulation Sensitizes Prostate Cancer Cells to Chemotherapy

“…Therefore, our goal was to develop an efficient nanoplatform to deliver miR-205 in its native form to cancer cells ( Figure 1 , Figure 2 and Figure 3 ). Poly(ethyleneimine) or cationic-based polymer delivery of miRNAs have inherent higher transfection efficiency via a proton sponge effect at low pH in the endo/lysosomal compartments where it induces membrane-rupture, resulting in the release of miRNAs into the cytoplasm [ 42 ]. Our formulation has a slightly positive charge (particle size, ~100 nm), which is highly suitable for miRNAs delivery due to its ability of penetrating tumor sites through leaky blood vessels.…”

The Role of MicroRNAs in Repair Processes in Multiple Sclerosis

“…Combining stem cell and biomaterial approaches, implantation of human endometrial stem cells encapsulated in a fibrin hydrogel scaffold is associated with improved motor recovery in SCI, and when the stem cells were further engineered to overexpress miR-219 remyelination also improved [ 137 ]. Finally, in a peripheral model of sciatic nerve crush, a biodegradable and biocompatible cationic polymer generated from polyethyleneimine cross-linked with 2,6-pyridinedicarboxaldehyde was loaded with miR-221/miR-222 and used to transfect Schwann cells, promoting MBP synthesis and remyelination [ 138 ].…”

Immune Activities of Polycationic Vectors for Gene Delivery

“…The conventional method used to solve the problem of inherent immunogenicity of polycations is the modification of their structure, in which chemical modification is the most common approach. For example, modifying the two ends or the side chains (Thomas and Klibanov, 2002 ; Arote et al, 2007 ; Yang et al, 2015 ), changing the degree or synthetic methods of polymerization (Kukowska-Latallo et al, 1996 ; Yu et al, 2016 ) and modifying the backbone of polycations by adding cross-linking agents (Wang et al, 2002 ; He et al, 2015 ; Che et al, 2016 ; Song et al, 2016 , 2017 ) have been tried to modify the chemical structure of polycations. Modification of chemical structures has been widely used to lower the toxicity of polycations, and actually it did make some excellent achievements.…”