| dc.description.abstract | Drug delivery is a promising therapeutic approach to achieve sustainable drug release while minimizing adverse side effects triggered by non-specificity of the free drugs. Among delivery vectors, biodegradable nanomaterials are of utmost interest for minimizing deleterious consequences stemming from long-term carrier accumulation. With regard to inorganic nanomaterials, porous silicon (pSi) is among a few that can degrade and release non-toxic byproducts (i.e. orthosilicic acid), and dissolution kinetics of the materials can readily be controlled via modulating structural morphology as well as surface chemistry. To date, a great number of pSi-based delivery vectors with intricate designs have been presented to address multiple challenges in therapeutic delivery. Since the shape of the nanocarriers have been shown to influence interactions with multiple biological components, pSi with various geometrical shapes (i.e. discoidal, hemisphere and platelet shapes) have been introduced in recent years, and promising therapeutic efficacy has also been demonstrated in various disease models. Recently, via a sacrificial ZnO template method developed by our group, we have shown that one-dimensional (1D) porous nanotube structure of Si (pSiNTs) with well-defined shell thickness, inner diameter and length can readily be achieved. Since the materials can degrade in biological media and exert negligible effects to viability of both normal (e.g. human embryonic kidney, HEK 293) and cancer (e.g. HeLa cervical cancer) human cells, it is of great interest to evaluate pSiNTs as potential therapeutic platforms. Interestingly, we have also demonstrated pSiNTs can also serve as a facile template for facilitating formation of a secondary nanostructure, so called platinum nanocrystals (Pt NCs) with potential anti-cancer properties. Evaluation of in vitro anti-cancer activity of this novel nanohybrid revealed the viability of HeLa cells was reduced in a time-dependent manner as a consequence of a “Trojan horse” mechanism, in which a high concentration of Pt NCs are internalized within cells assisted by pSiNTs and subsequently released via dissolution of the nanotube matrix. In addition, pSiNTs are also evaluated as potential therapeutic delivery vectors for nucleic acids. Preliminary in vitro studies suggest the materials can deliver reporter plasmids DNA (circular DNA) encoding green fluorescent proteins (eGFP) into HEK 293 cells. In another study, downregulations of eGFP (in HeLa) and estrogen receptors (ER) (in MCF-7 breast cancer cells) are also demonstrated via delivery of small interfering RNA (siRNAs) targeting eGFP-mRNA (siGFP) and ER-mRNA (siER) by pSiNTs. All in all, these studies presented herein demonstrate the potential merit of pSiNTs in drug delivery and serve as a foundation for future studies to design pSiNTs-based platforms that can successively address multiple biological barriers encountered upon systemic administration. Such studies expand the library of possible pSi structures in nanomedicine for suitable disease models and associated applications. | |
