Poly-l-lysine Functionalized Large Pore Cubic Mesostructured Silica Nanoparticles as Biocompatible Carriers for Gene Delivery

Abstract

Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-l-lysine (PLL) were designed as a new carrier material for gene delivery applications. The synthesized LP-MSNs are 100–200 nm in diameter and are composed of cage-like pores organized in a cubic mesostructure. The size of the cavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto the silica surface through covalent immobilization was confirmed by X-ray photoelectron spectroscopy, solid-state 13C magic-angle spinning nuclear magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis. As a result of the particle modification with PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs was observed compared to the native unmodified silica particles. Consequently, PLL-functionalized nanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as gene carriers compared to amino-functionalized nanoparticles and the native nanoparticles. The system was tested to deliver functional siRNA against minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated great potential for efficient gene transfer into cancer cells as a decrease of the cellular viability of the osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles also exhibit a high biocompatibility, with low cytotoxicity observed up to 100 μg/mL.

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

“…Hence, in a nice approach for siRNA delivery by Hartono et al, cubic LP-MSNs materials with pore sizes around 13.4 nm were functionalized with a biocompatible polylysine peptide. 109 As expected, the magnitude of polypeptide chain played a double and divergent behaviour, because DNA adsorption and toxicity by membrane destabilization were increased directly with the number of positive charges. The chosen siRNA sequences PLK (sense) 5'-(CCA UUA ACG AGC UGC UUA ATT)-3';PLK (antisense) 5'-(UUA AGC AGC UCG UUA AUG GTT)-3'; Mirk (sense) 5'-(GGC ACU UCA UGU UCC GGA ATT)-3'; Mirk (antisense) 5'-(UUC CGG AAC AUG AAG UGC CGC)-3', S10 (sense) 5'-(GCA ACA GUU ACU GCG ACG UUU)-3'; and S10 (antisense) 5'-(ACG UCG CAG UAA CUG UUG CUU)-3' were successfully adsorbed onto the polylysine functionalized LPMSNs.…”

“…Among all known peptides, the most recurrent examples for gene delivery purposes are polylysine 109 and the KALA fusogenic peptide. 106 Nevertheless, there have been also designed other interesting peptides able to efficiently interact with siRNAs.…”

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

“…There are many examples of the functionalization of AuNPs [94,95], MNPs [54,[96][97][98], SiNPs [61,99,100], with PEI of different molecular weights [61,101] or even modified with labile bonds like acetal [102]. In relation to the PLL, this polymer has been used previously modified with a terminal cysteine for the direct attachment to AuNPs [103], conjugated to epoxysilanes [62] and as part of a layer-by-layer system with siRNA [104]. However, more polymers have been used for conjugation, e.g.…”

Study on the use of 3‐aminopropyltriethoxysilane and 3‐chloropropyltriethoxysilane to surface biochemical modification of a novel low elastic modulus Ti–Nb–Hf alloy

“…This problem can be overcome, at least in part, by adding a preliminary activation treatment. For pure titanium, there is a large diversity of examples in the literature suggesting different activation methods to provide reactive groups for covalent immobilization of biomolecules (mainly -OH groups) [2][3][4][5][6][7][8][9][10][11] and organosilanes bearing different functional groups [12][13][14][15][16][17]. Recently, a comparative study between two activation methods frequently used (Oxygen plasma and Piranha solution) was performed by V. Paredes [18].…”

“…Nowadays, organosilane precursors bearing functional groups such as amino [12][13][14][15][16][17][18][19][20][21][22], thiol, carboxyl, phosphate, vinyl [23][24][25], cyanide [26], phenyl [24,27] or sulphhydryl groups are readily available. Despite the wide variety of silane precursors available for surface modification, the majority of studies have employed aminosilanes, in particular 3-aminopropyltriethoxysilane (APTES) [11][12][13][14][15][16][17][18][19][20][21][22]. Nevertheless, the 3-chloropropyltriethoxysilane (CPTES) is also proposed by other authors [2,4,10].…”