Carbonate apatite-facilitated intracellularly delivered siRNA for efficient knockdown of functional genes

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

“…Among them polycationic polymers based on polyethylene imine (PEI) [3], dendrimers [4], chitosan derivatives [5,6] and polylysine [7] form nanometric complexes (polyplexes) with pDNA and siRNA have already demonstrated to enhance the uptake of the associated nucleotides [4]. But despite their ability to enhance the cellular uptake of condensed siRNA, they still exhibit low knockdown efficiency due to insufficient siRNA release [8]. Recently, high knockdown efficiency was indeed reported for branched polyaminoamides, but the employed solid-phase synthesis is difficult to scale up [9].…”

“…After demonstrating delivery of pDNA we focused on the delivery of siRNA, for its implications in the RNA interference (RNAi) therapy of diseases like cancer [8] and tuberculosis etc. [30].…”

Nanoparticle-facilitated Intratumoral Delivery of Bcl-2/IGF-1R siRNAs and p53 Gene Synergistically Inhibits Tumor Growth in Immunocompetent Mice

“…It should be noted that we had extensively analyzed the morphology, size distribution and zeta potential of carbonate apatite nanoparticles by transmission electron microscope (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS) and zeta sizer in our earlier publications. Moreover, we had reported on siRNA binding affinity towards the nanoparticles, cellular uptake and knockdown efficacy using reporter gene assays [32][33][34][35][36][37][38]. We have therefore not included those data in the current manuscript.…”

“…A number of existing non-viral vectors are available for intracellular delivery of siRNA and plasmid DNA to silence the target mRNA of a particular gene and to express a protein of interest, respectively, with limitations in proper condensation, cellular uptake and endosomal escape, leading to a decrease in overall performance of the delivered siRNA or DNA [30,31]. Recently, we developed pH-responsive carbonate apatite nanoparticles to efficiently deliver siRNA as well as DNA across the cell membrane and facilitate them to release from the particles and endosomal vesicles to carry out knockdown of a specific mRNA transcript or expression of a desirable protein, respectively [32,33]. Moreover, we demonstrated nanoparticleassisted delivery of the siRNAs targeting cyclin B1, PLC-gamma-2/ calmodulin 1, HER2/ErbB2, ABCG2/ABCB1 and cROS1 mRNAs sensitizes cervical adenocarcinoma and breast cancer cells towards traditional anti-cancer drugs [34][35][36][37][38].…”

Nanoparticles and Toxicity in Therapeutic Delivery: the Ongoing Debate

“…future science group siRNA-apatite complexes, following endocytosis, are very quickly almost completely dissolved below pH 7.0 [24]. This might have contributed to the destabilization of endosomes, resulting in the quick escape of therapeutics from the endo/lysosome in a short timeframe.…”