<p>Inhibition of proliferation and migration of tumor cells through phenylboronic acid-functionalized polyamidoamine-mediated delivery of a therapeutic DNAzyme Dz13</p>

Abstract

Background The phenylboronic acid-functionalized polyamidoamine (PP) was employed as a gene carrier for Dz13 delivery, inducing an obvious anticancer response. Materials and methods The Dz13 condensation ability of PP was evaluated through gel retardation assay. The cellular uptake mechanism of PP/Dz13 nanoparticles was studied using confocal laser scanning microscope and flow cytometer. The inhibition ability of cell proliferation, migration and invasion was investigated through MTT assay, flow cytometry, wound healing and Transwell migration assays, using hepatocarcinoma cell line HepG2 as a model. Finally, Western blotting analysis was used to detect the signaling pathway associated with the inhibition of cell apoptosis and migration induced by Dz13 delivery. Results The carrier PP could efficiently condense Dz13 into stable nanoparticles at mass ratios of >1.5. The hydrodynamic diameter and zeta potential of PP/Dz13 nanoparticles were measured to be 204.77 nm and +22.00 mV at a mass ratio of 10.0, respectively. The nanoparticles could realize an efficient cellular uptake in sialic acid-dependent endocytosis manner. Moreover, the nanoparticles exhibited an obvious antiproliferation effect through the induction of cell apoptosis and cell cycle arrest due to the cleavage of c-Jun mRNA. Besides, the suppression of cell migration and invasion could be achieved after the PP/Dz13 transfection, attributing to the decreased expression level of MMP-2 and MMP-9 . Conclusion The PP provided a potential delivery system to achieve the tumor-targeting gene therapy.

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

“…In the apoptotic pathways, caspase-8 has been identified to execute the cell death receptor-mediated apoptosis, whereas the activation of caspase-9 has been considered as the initiator of mitochondria-dependent apoptosis signaling pathway. 56 The data implied that both apoptotic routes could be activated by MDPAS micelles, thereby leading to the antiproliferative effect in cancer cells.…”

Phenylboronic Acid-Modified Polyamidoamine Mediated the Transfection of Polo-Like Kinase-1 siRNA to Achieve an Anti-Tumor Efficacy

“…After the incubation in 10% FBS-containing DMEM for 48 h, MTT solution was added into each well at a final concentration of 0.5 mg/mL, and the plates were incubated at 37 °C for 4 h. Then, 150 µL dimethyl sulfoxide was added to dissolve the formazan crystals, and the optical density at 520 nm was detected using an HBS-1096A microplate reader (Detie, Nanjing, China) to calculate the cell viability according to the previous reports. 34 , 35 For the colony formation assay, the cells after siPlk-1 transfection were plated in 6-well plates at a density of 1.0×10 4 cells/well and incubated at 37 °C for 7 days. Then, the cells were washed with PBS three times, fixed in 75% ethanol and stained with 0.2% crystal violet.…”

“…[30][31][32][33][34] In our previous reports, phenylboronic acid (PBA) was conjugated on the surface of PAMAM to construct two types of tumor-targeted derivatives which were employed as carriers to facilitate the delivery of oligonucleotides including miR-34a, DNAzyme and short GC rich DNA. [33][34][35] PBA has been considered as an effective ligand which specifically recognizes the sialic acids overexpressed in various tumor cells. 36,37 After the modification with PBA, the derivatives could acquire the tumor-targeted ability and achieve favorable gene transfection via the sialic acid-dependent endocytosis pathway.…”

Fluoropolymer‐Mediated Intracellular Delivery of miR‐23b for the Osteocyte Differentiation in Osteoblasts

“…To date, a variety of strategies have been adopted to achieve these goals. For instance, the amine groups in PAMAM have been modified using nucleobase analog, [ 22,23 ] amino acids, [ 24 ] phenylboronic acid, [ 25–27 ] chondroitin sulfate, [ 28 ] and lactobionic acid. [ 29 ] Other than these methods, fluorination is a widely accepted method that significantly improves the transfection efficacy of DNA, siRNA, miRNA, proteins, and peptides owing to the presence of a unique fluorine effect during transfection.…”