A Calcium Phosphate Nanoparticle-Based Biocarrier for Efficient Cellular Delivery of Antisense Oligodeoxynucleotides

Abstract

Antisense oligodeoxynucleotides (ASODNs) can bind to some specific RNA of survivin can prevent the mRNA translation at the genetic level, which will inhibit survivin expression and make the cancer cells apoptosis. However, the ASODNs-based therapies are hampered by their instability to cellular nuclease and their weak intracellular penetration. Here we reported a calcium phosphate (CP)-based carrier to achieve efficient delivery of ASODNs into cells. In this study, we used a facile microemulsion approach to prepare spherical and porous ASODNs-CP nanoparticles (ASODNS-CPNPs) with the size of 50-70 nm in diameter, and their structure, morphology and composition were characterized by TEM, XRD, FTIR, ICP and DLS, UV-Vis spectroscopy and agarose gel electrophoresis. The results indicated that the nanoparticles have a high ASODNs loading capacity. Furthermore, cellular uptake and delivery efficiency of the ASODNS-CPNPs, as well as cellular apoptosis induced by the ASODNs doping into the calcium phosphate nanoparticles, were investigated by confocal laser scanning microscopy, biological TEM, flow cytometry, and MTT assay. Efficient intracellular delivery of the nanoparticles was observed. All these results suggested that the prepared calcium phosphate nanoparticles could be used as a promising biocarrier for delivery of ASODNs.

Enhanced antineoplastic/therapeutic efficacy using 5-fluorouracil-loaded calcium phosphate nanoparticles

“…The synthesized CaP@5-FU NPs were characterized with UV–vis spectroscopy over a range of 200 to 800 nm. The spectrum obtained displayed a characteristic peak at 230 nm [ 25 ] for unloaded CaP NPs and CaP@5-FU NPs as shown in Fig. 1 .…”

“…Cancer cells flourish in an acidic microenvironment, which enhances the tumour progression by evading the normal immune response and metastasis development. The secretion of lactate in the anaerobic glycolysis (with CO 2 as a by-product of the metabolism) hypoxia environment results in the acidic microenvironment [ 25 ].…”

Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy

“…Oligodeoxynucleotides have also been efficiently delivered into cells by a calcium phosphate (CP)-based carrier, developed by Hou and coworkers. The spherical porous ODN-CP nanoparticles with a diameter of 50-70 nm used in this case were prepared by a facile microemulsion approach (Hou et al, 2013). Fabrication of micro-and nanoparticles with defined features, such as shape, size, surface charge, stiffness, and chemical composition, can also be performed by a high-resolution molding technology known as particle replication in non-wetting templates.…”

Carbon Nanodots Doped Super-paramagnetic Iron Oxide Nanoparticles for Multimodal Bioimaging and Osteochondral Tissue Regeneration via External Magnetic Actuation

“…The band gap of the powder was determined using the standard protocol reported previously using the standard absorbance spectrum of sucrose derived CDs, calcium phosphate nanoparticles already reported in the literature. − The measurement was conducted using the formulas mentioned below. ­[ E = band gap energy (eV); h = Planck’s constant (6.626 × 10 –34 J s); C = Velocity of light at vacuum (3 × 10 8 m/s); λ = cutoff wavelength in UV–vis spectrum (nm)]…”