Nerve Growth Factor-Conjugated Mesoporous Silica Nanoparticles Promote Neuron-Like PC12 Cell Proliferation and Neurite Growth

Abstract

Therapeutic strategies to promote nerve cell growth and improve their functions or stimulate nerve fiber reconnection and ameliorate the loss of neuronal functions are in high demand. A disadvantage of current conventional methods, which includes injection of nerve growth factors (NGF) either systemically or in the affected area, is rapid clearance or degradation of NGF, thereby reducing the effective concentration of NGFs that can reach the damaged nerves to stimulate the healing process. To overcome this obstacle, a nanoparticle platform based on mesoporous silica nanoparticles (MSNs) was developed to not only prevent clearance and degradation of NGFs, but also deliver the NGF directly to nerve cells to promote nerve cell proliferation and neurite growth. We synthesized (NGF)-loaded MSN (MSN-NGF) with a diameter of 65 nm. MSN-NGF significantly promoted the differentiation of neuron-like PC12 cells and growth of neurites compared to NGF alone, as confirmed by MTS cell proliferation assay and optical microscopy analysis. This study shows that MSN-NGF could be an effective therapy to speed up nerve cell growth or recovery of function.

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

“…Inorganic and polymer nanoparticles, and hydrogels are well known platforms for NGF delivery . In the year 2016, Sun et al reported on the synthesis of MSNs with a diameter of 65 nm and had conjugated NGFs onto the surface of MSNs as an effective therapy to stimulate nerve healing . They compared the differentiation and proliferation of neurites arising from PC12 cells reacted with MSN‐NGFs with PC12 cells treated with only free NGFs and with free MSNs, they performed MTS assay and evaluated their viability after exposing for 72 h. According to the authors, the PC12 neurosecretory cell line is known for its uniformity and reproducibility when used as a neuronal differentiation model .…”

“…They compared the differentiation and proliferation of neurites arising from PC12 cells reacted with MSN‐NGFs with PC12 cells treated with only free NGFs and with free MSNs, they performed MTS assay and evaluated their viability after exposing for 72 h. According to the authors, the PC12 neurosecretory cell line is known for its uniformity and reproducibility when used as a neuronal differentiation model . Their studies revealed that MSN‐NGFs were able to significantly promote PC12 generation and neurite growth compared to free NGFs alone . The lengths of neurites were significantly elongated when PC12 cells were exposed to NGF loaded silica nanoparticles.…”

Impact of nanoparticles on neuron biology: current research trends

“…[27][28][29][30][31][32][33][34][35][36][37][38] In addition, interests have also been generated to study the effects of nanoparticles on neurons and there are several reports that suggest that nanoparticles promote neuronal differentiation, and neuroprotection studied in both in vitro and in vivo conditions. 3,[39][40][41][42][43] To get better therapeutic results, various types of nanoparticles have been studied in neurons, and among those, carbon-based nanoparticles are mostly reported, 4,[44][45][46][47][48] followed by gold and silver nanoparticles (AgNPs). [49][50][51] Despite having many beneficial properties, nanoparticle also raises few health hazard and toxicity issues.…”

Single/Dual Alkaline Earth Metal‐Doped Hollow Nanoparticles as Nanocarrier for Accelerating Neurite Development by Activating pERK and pJNK

“…Enzyme‐linked immunosorbent assays (ELISAs) were performed to determine the amount of encapsulated NGF. This assay established that ≈2.04 µg of NGF was loaded per mg of AEM‐HNPs; this loading efficiency is 3.07 times higher than that reported for other NGF‐conjugated mesoporous silica nanoparticle‐based systems lacking the hollow morphology of the carrier . Also, the release profile of NGF from the N+AEM‐HNPs was exploited by dispersing them in two types of solvents, that is, hydrophilic phosphate buffer saline (PBS) and hydrophobic DMSO (Figure S3, Supporting Information).…”