ABSTRACT
Porous silicon nanoparticles (pSiNPs) have gained attention from drug delivery systems (DDS) due to their biocompatibility, high drug-loading efficiency, and facile surface modification. To date, many surface chemistries of pSiNPs have been developed to maximize the merits and overcome the drawbacks of pSiNPs. In this work, we newly disclosed a formulation, iron-silicate-coated pSiNPs (Fe-pSiNPs-NCS), using the surface modification method with iron-silicate and 3-isothiocyanatopropyltriethoxysilane (TEPITC). Fe-pSiNPs-NCS demonstrated effective reactive-oxygen species (ROS) self-generation ability via a Fenton-like reaction of iron-silicate and in situ hydrogen peroxide (H2O2) generation of TEPITC on the surface of pSiNPs, resulting in excellent anticancer effect in U87MG cancer cells. Moreover, we confirmed that Fe-pSiNPs-NCS could be used as a drug delivery carrier as it was proven that anticancer drugs (doxorubicin, SN-38) were loaded into Fe-pSiNPs-NCS with high-loading efficiency. These findings could offer efficient strategies for developing nanotherapeutics in biomedical fields.
Subject(s)
Nanoparticles , Silicon , Silicon/pharmacology , Reactive Oxygen Species , Iron , Porosity , Hydrogen Peroxide , Silicates , Drug Carriers , Silicon DioxideABSTRACT
There has been a lot of basic and clinical research on Alzheimer's disease (AD) over the last 100 years, but its mechanisms and treatments have not been fully clarified. Despite some controversies, the amyloid-beta hypothesis is one of the most widely accepted causes of AD. In this study, we disclose a new amyloid-beta plaque disaggregating agent and an AD brain-targeted delivery system using porous silicon nanoparticles (pSiNPs) as a therapeutic nano-platform to overcome AD. We hypothesized that the negatively charged sulfonic acid functional group could disaggregate plaques and construct a chemical library. As a result of the in vitro assay of amyloid plaques and library screening, we confirmed that 6-amino-2-naphthalenesulfonic acid (ANA) showed the highest efficacy for plaque disaggregation as a hit compound. To confirm the targeted delivery of ANA to the AD brain, a nano-platform was created using porous silicon nanoparticles (pSiNPs) with ANA loaded into the pore of pSiNPs and biotin-polyethylene glycol (PEG) surface functionalization. The resulting nano-formulation, named Biotin-CaCl2-ANA-pSiNPs (BCAP), delivered a large amount of ANA to the AD brain and ameliorated memory impairment of the AD mouse model through the disaggregation of amyloid plaques in the brain. This study presents a new bioactive small molecule for amyloid plaque disaggregation and its promising therapeutic nano-platform for AD brain-targeted delivery.
ABSTRACT
Porous silicon (pSi) materials have gained a great deal of attention from various research fields, and their surface-functionalization is one of the critical points for their applications. In this study, a new surface modification method of Si-H-terminated pSi materials via microwave-induced Si-S bond formation is disclosed. The silicon hydride (Si-H) functionality on the pSi surface could react with the 5-membered cyclic disulfide (S-S) compound (DL-α-lipoic acid in this study) by microwave-induced in situ S-S bond cleavage and Si-S bond formation. This surface chemistry is fast responsive (<10 min) and more efficient than other methods such as vortexing, heating stirring, or ultrasonication. The reaction maintains the primary porous structure of pSi materials including pSi wafer, pSi rugate filer, and pSi nanoparticles. An additional functional group such as carboxylic acid is demonstrated to be readily introducible on the pSi surface for further applications. Overall, this study has successfully demonstrated the porous silicon surface modification via a microwave-induced in situ cyclic disulfide (S-S) cleavage and Si-S bond formation.
