Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles

Abstract

In this research we employed layered double hydroxide nanoparticles (LDHs) to simultaneously deliver an anticancer drug 5-fluorouracil (5-FU) and Allstars Cell Death siRNA (CD-siRNA) for effective cancer treatment. The strategy takes advantage of the LDH anion exchange capacity to intercalate 5-FU into its interlayer spacing and load siRNA on the surface of LDH nanoparticles. LDH nanoparticles have been previously demonstrated as an effective cellular delivery system for 5-FU and siRNA separately in various investigations. More excitedly, the combination of CD-siRNA and anticancer drug 5-FU with the same LDH particles significantly enhanced cytotoxicity to three cancer cell lines, e.g. MCF-7, U2OS and HCT-116, compared to the single treatment with either CD-siRNA or 5-FU. This enhancement is probably a result of coordinate mitochondrial damage process. Thus, the strategy to co-deliver siRNA and an anticancer drug by LDHs has great potential to overcome the drug resistance and enhance cancer treatment.

Inorganic nanolayers: structure, preparation, and biomedical applications

“…173 The LDH-based sustained codelivery of 5-FU and siRNAs markedly enhanced anticancer activity in comparison to single treatment of either of the two against three cancer cell lines, namely human breast (MCF-7), osteosarcoma (U2OS), and colorectal . 173 This codelivery formulation has the strong potential to overcome the emergence of drug-resistant cancer.…”

Impact of size, secondary structure, and counterions on the binding of small ribonucleic acids to layered double hydroxide nanoparticles

“…24 Delivery of ribonucleic acid (RNA) molecules into cells after intercalation into HT has not been studied as intensively as delivery of DNA, but a few studies exist. 12,15,25,26 Interestingly, Li et al demonstrated that the combination of short interfering RNA (siRNA) and anticancer drugs such as 5-FU loaded onto HT enhances the delivery efficiency into cancerous cells, demonstrating a potential advantage of combining drugs with biomolecules for cancer therapy using nanoclays. 26 RNA interference (RNAi) is a silencing mechanism that occurs in eukaryotic cells as a protein synthesis regulation event.…”

“…12,15,25,26 Interestingly, Li et al demonstrated that the combination of short interfering RNA (siRNA) and anticancer drugs such as 5-FU loaded onto HT enhances the delivery efficiency into cancerous cells, demonstrating a potential advantage of combining drugs with biomolecules for cancer therapy using nanoclays. 26 RNA interference (RNAi) is a silencing mechanism that occurs in eukaryotic cells as a protein synthesis regulation event. [27][28][29][30] This process is intricately linked to the silencing that derives from microRNAs (miRNAs).…”

Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways

“…The DLS data in Figures 1C and 1D indicated that the average size of LDH nanoparticles was ~109 nm with a zeta potential of +42.9 mV, consistent with our previous reports. 15 After loading 5-FU into LDH nanoparticles, LDH-5-FU nanohybrids presented a narrow particle size distribution in the range of 50-150 nm and a zeta potential of +40.6 mV ( Figures 1C and 1D). Compared with LDH, the average size of LDH-5-FU decreased from 109 nm to 85 nm, as reported previously, 15 due to inhibition of the hydroxide layer growth by the anionic 5-FU.…”

“…15 After loading 5-FU into LDH nanoparticles, LDH-5-FU nanohybrids presented a narrow particle size distribution in the range of 50-150 nm and a zeta potential of +40.6 mV ( Figures 1C and 1D). Compared with LDH, the average size of LDH-5-FU decreased from 109 nm to 85 nm, as reported previously, 15 due to inhibition of the hydroxide layer growth by the anionic 5-FU. The TEM image in Figure 1B shows that the LDH-5-FU nanohybrid had a similar platelike morphology to the LDH nanoparticle.…”