Cross-linked polyethylenimine–tripolyphosphate nanoparticles for gene delivery

Abstract

The high transfection efficiency of polyethylenimine (PEI) makes it an attractive potential nonviral genetic vector for gene delivery and therapy. However, the highly positive charge of PEI leads to cytotoxicity and limits its application. To reduce the cytotoxicity of PEI, we prepared anion-enriched nanoparticles that combined PEI with tripolyphosphate (TPP). We then characterized the PEI-TPP nanoparticles in terms of size, zeta potential, and Fourier-transform infrared (FTIR) spectra, and assessed their transfection efficiency, cytotoxicity, and ability to resist deoxyribonuclease (DNase) I digestion. The cellular uptake of PEI-TPP with phosphorylated internal ribosome entry site–enhanced green fluorescent protein C1 or FAM (fluorouracil, Adriamycin [doxorubicin] and mitomycin)-labeled small interfering ribonucleic acids (siRNAs) was monitored by fluorescence microscopy and confocal laser microscopy. The efficiency of transfected delivery of plasmid deoxyribonucleic acid (DNA) and siRNA in vitro was 1.11- to 4.20-fold higher with the PEI-TPP particles (7.6% cross-linked) than with the PEI, at all N:P ratios (nitrogen in PEI to phosphorus in DNA) tested. The cell viability of different cell lines was more than 90% at the chosen N:P ratios of PEI-TPP/DNA complexes. Moreover, PEI-TPP nanoparticles resisted digestion by DNase I for more than 2 hours. The time-dependent absorption experiment showed that 7.6% of cross-linked PEI-TPP particles were internalized by 293T cells within 1 hour. In summary, PEI-TPP nanoparticles effectively transfected cells while conferring little or no toxicity, and thus have potential application in gene delivery.

Targeting Polymeric Nanobiomaterials as a Platform for Cartilage Tissue Engineering

“…In recent years gene therapy has been widely investigated for the treatment of OA and has proved to be a promising alternative because it allows treating the causes instead of the symptoms [152]. Viral and nonviral systems can be used, but viral systems, despite their high transfection efficiency and which allow the protection of deoxyribonucleic acid (DNA) against enzymatic attack, have the disadvantage of generating an undesired immune response [153]. Then, non-viral administration systems are viable candidates for the treatment of osteoarthritis.…”

“…The biological factors that regulate cartilage degeneration in OA are diverse, including: NF-κB, HIF-2α, interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinases (MMP) and disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) [153][154][155]. These factors are an important group of therapeutic targets for the action of vectors in gene therapy for the of OA.…”

Safe Nanocomposite‐Mediated Efficient Delivery of MicroRNA Plasmids for Autosomal Dominant Polycystic Kidney Disease (ADPKD) Therapy

“…Nanoparticles (NPs) had been shown to effectively increase pDNA delivery to target cells or tissues . In addition to highly efficient gene delivery, another advantage of using NPs as a carrier is that NPs can protect pDNA against DNase digestion in blood circulation following intravenous injection . To date no combination of miRNA plasmids and nanomaterials has been proposed to treat ADPKD.…”

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

“…Lots of works have been done about cross-linked low molecular weight PEI in our previous research. 23,24 In this study, we cross-linked PEI1.8kDa with 2,6-pyridinedicarboxaldehyde (PDA) to develop a biodegradable low molecular weight cationic polymer (PDAPEI), which showed a higher transfection efficiency and a relatively low cytotoxicity in various cell lines.…”