Codelivery of Plasmid and Curcumin with Mesoporous Silica Nanoparticles for Promoting Neurite Outgrowth
Journal
ACS Applied Materials and Interfaces
Journal Volume
11
Journal Issue
17
Pages
15322-15331
Date Issued
2019
Author(s)
Abstract
Reactive oxygen species (ROS)-induced oxidative stress leads to neuron damage and is involved in the pathogenesis of chronic inflammation in neurodegenerative diseases (NDs), such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Researchers, therefore, are looking for antiinflammatory drugs and gene therapy approaches to slow down or even prevent neurological disorders. Combining therapeutics has shown a synergistic effect in the treatment of human diseases. Many nanocarriers could be designed for the simultaneous codelivery of drugs with genes to fight diseases. However, only a few researches have been performed in NDs. In this study, we developed a mesoporous silica nanoparticle (MSN)-based approach for neurodegenerative therapy. This MSN-based platform involved multiple designs in the targeted codelivery of (1) curcumin, a natural antioxidant product, to protect ROS-induced cell damage and (2) plasmid RhoG-DsRed, which is associated with the formation of lamellipodia and filopodia for promoting neurite outgrowth. At the same time, TAT peptide was introduced to the plasmid RhoG-DsRed via electrostatic interaction to elevate the efficiency of nonendocytic pathways and the nuclear plasmid delivery of RhoG-DsRed in cells for enhanced gene expression. Besides, such a plasmid RhoG-DsRed/TAT complex could work as a noncovalent gatekeeper. The release of curcumin inside the channel of the MSN could be triggered when the complex was dissociated from the MSN surface. Taken together, this MSN-based platform combining genetic and pharmacological manipulations of an actin cytoskeleton as well as oxidative stress provides an attractive way for ND therapy. ? 2019 American Chemical Society.
Subjects
codelivery; combining therapy; mesoporous silica nanoparticles; neurite growth; neurodegenerative diseases
SDGs
Other Subjects
Controlled drug delivery; DNA; Gene expression; Gene therapy; Mesoporous materials; Nanoparticles; Neurodegenerative diseases; Proteins; Silica; Silica nanoparticles; Targeted drug delivery; Amyotrophic lateral sclerosis; Co deliveries; combining therapy; Enhanced gene expression; Mesoporous silica nanoparticles; Neurite growth; Pharmacological manipulation; Reactive oxygen species; Anti-inflammatory drugs; Disease control; curcumin; drug carrier; guanosine triphosphatase; nanoparticle; peptide fragment; reactive oxygen metabolite; silicon dioxide; transactivator protein; actin filament; animal; chemistry; drug effect; genetics; metabolism; mouse; neurite outgrowth; oxidative stress; particle size; plasmid; porosity; tumor cell line; Actin Cytoskeleton; Animals; Cell Line, Tumor; Curcumin; Drug Carriers; GTP Phosphohydrolases; Mice; Nanoparticles; Neuronal Outgrowth; Oxidative Stress; Particle Size; Peptide Fragments; Plasmids; Porosity; Reactive Oxygen Species; Silicon Dioxide; tat Gene Products, Human Immunodeficiency Virus
Type
journal article