Porous silicon in drug delivery devices and materials

Semiconductor nanowires (NWs) have been studied extensively for over two decades for their novel electronic, photonic, thermal, electrochemical and mechanical properties. This comprehensive review article summarizes major advances in the synthesis, characterization, and application of these materials in the past decade. Developments in the understanding of the fundamental principles of "bottom-up" growth mechanisms are presented, with an emphasis on rational control of the morphology, stoichiometry, and crystal structure of the materials. This is followed by a discussion of the application of nanowires in i) electronic, ii) sensor, iii) photonic, iv) thermoelectric, v) photovoltaic, vi) photoelectrochemical, vii) battery, viii) mechanical, and ix) biological applications. Throughout the discussion, a detailed explanation of the unique properties associated with the one-dimensional nanowire geometry will be presented, and the benefits of these properties for the various applications will be highlighted. The review concludes with a brief perspective on future research directions, and remaining barriers which must be overcome for the successful commercial application of these technologies.

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25th Anniversary Article: Semiconductor Nanowires – Synthesis, Characterization, and Applications

Among the numerous attempts to integrate tissue engineering concepts into strategies to repair nearly all parts of the body, neuronal repair stands out. This is partially due to the complexity of the nervous anatomical system, its functioning and the inefficiency of conventional repair approaches, which are based on single components of either biomaterials or cells alone. Electrical stimulation has been shown to enhance the nerve regeneration process and this consequently makes the use of electrically conductive polymers very attractive for the construction of scaffolds for nerve tissue engineering. In this review, by taking into consideration the electrical properties of nerve cells and the effect of electrical stimulation on nerve cells, we discuss the most commonly utilized conductive polymers, polypyrrole (PPy) and polyaniline (PANI), along with their design and modifications, thus making them suitable scaffolds for nerve tissue engineering. Other electrospun, composite, conductive scaffolds, such as PANI/gelatin and PPy/poly(e-caprolactone), with or without electrical stimulation, are also discussed. Different procedures of electrical stimulation which have been used in tissue engineering, with examples on their specific applications in tissue engineering, are also discussed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/term.383

Application of conductive polymers, scaffolds and electrical stimulation for nerve tissue engineering.

A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells using surface-modified vertical silicon nanowires. The method relies on the ability of the silicon nanowires to penetrate a cell’s membrane and subsequently release surface-bound molecules directly into the cell’s cytosol, thus allowing highly efficient delivery of biomolecules without chemical modification or viral packaging. This modality enables one to assess the phenotypic consequences of introducing a broad range of biological effectors (DNAs, RNAs, peptides, proteins, and small molecules) into almost any cell type. We show that this platform can be used to guide neuronal progenitor growth with small molecules, knock down transcript levels by delivering siRNAs, inhibit apoptosis using peptides, and introduce targeted proteins to specific organelles. We further demonstrate codelivery of siRNAs and proteins on a single substrate in a microarray format, highlighting this technology’s potential as a robust, monolithic platform for high-throughput, miniaturized bioassays.

https://www.pnas.org/content/pnas/107/5/1870.full.pdf

Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

/pdf/tumor-exosome-based-nanoparticles-are-efficient-drug-3qbogs1pdc.pdf

Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy.

This work describes the formation of porous composite materials based on a combination of bioactive mesoporous silicon and bioerodible polymers such as poly-caprolactone (PCL). The fabrication of a range of composites prepared by both salt leaching and microemulsion techniques are discussed. Particular attention to the influence of Si content in the composite on in vitro calcification assays are assessed. For each system, cytotoxicity and cellular proliferation are explicitly evaluated through fibroblast cell culture assays.

Porous silicon-based scaffolds for tissue engineering and other biomedical applications

Graphene oxide (GO), the most common derivative of graphene, is an exceptional nanomaterial that possesses multiple physical properties critical for biomedical applications. GO exhibits pH-dependent fluorescence emission in the visible/near-infrared, providing a possibility of molecular imaging and pH-sensing. It is also water soluble and has a substantial platform for functionalization, allowing for the delivery of multiple therapeutics. GO physical properties are modified to enhance cellular internalization, producing fluorescent nanoflakes with low (<15%) cytotoxicity at the imaging concentrations of 15 μg/mL. As a result, at lower flake sizes GO rapidly internalizes into HeLa cells with the following 70% fluorescence based clearance at 24 h, assessed by its characteristic emission in red/near-IR. pH-dependence of GO emission is utilized to provide the sensing of acidic extracellular environments of cancer cells. The results demonstrate diminishing green/red (550/630 nm) fluorescence intensity ratios for HeLa and MCF-7 cancer cells in comparison to HEK-293 healthy cells suggesting a potential use of GO as a non-invasive optical sensor for cancer microenvironments. The results of this work demonstrate the potential of GO as a novel multifunctional platform for therapeutic delivery, biological imaging and cancer sensing.

/pdf/graphene-oxide-as-a-multifunctional-platform-for-21wnl2y4x0.pdf

Graphene Oxide as a Multifunctional Platform for Intracellular Delivery, Imaging, and Cancer Sensing.

In this study, the fabrication and characterization of highly porous composites composed of poly(e-caprolactone) and bioactive mesoporous silicon (BioSilicon) prepared using salt-leaching and microemulsion/freeze-drying methods are described. The role of silicon, along with porosity, in the scaffolds on calcium phosphate deposition was assessed using acellular in vitro calcification analyses. The presence of bioactive silicon in these scaffolds is essential for the deposition of calcium phosphate while the samples are immersed in simulated body fluid (SBF). Silicon-containing scaffolds produced using salt-leaching methods are more likely to calcify as a consequence of SBF exposure than those produced using microemulsion methods. In vitro proliferation and cell viability assays of these porous composites using human embryonic kidney fibroblast cells indicate that no cytotoxic effects are present in the scaffolds under the conditions used. Preliminary analyses of bone sialoprotein and alkaline phosphatase e...

High-Porosity Poly(ε-Caprolactone)/Mesoporous Silicon Scaffolds: Calcium Phosphate Deposition and Biological Response to Bone Precursor Cells

Despite significant advances of nanomedicine, the issues of biocompatibility, accumulation-derived toxicity, and the lack of sensing and in vivo imaging capabilities hamper the translation of most nanocarriers into clinic To address this, we utilize nitrogen, boron/nitrogen, and sulfur-doped graphene quantum dots (GQDs) as fully biocompatible multifunctional platforms allowing for multicolor visible/near-IR imaging and cancer-sensing These GQDs are scalably produced in one-step synthesis from a single biocompatible glucosamine precursor, are water-soluble, show no cytotoxicity at high concentrations of 1 mg/mL, and demonstrate substantial degradation at 36 h in biological environments as verified by TEM imaging Because of their small sizes, GQDs exhibit efficient internalization maximized at 12 h followed by further degradation/excretion Their high-yield intrinsic fluorescence in blue/green and near-infrared allows for multicolor in vitro imaging on its own or in combination with other fluorophores, and offers the capabilities for in vivo near-IR fluorescence tracking Additionally, nitrogen- and sulfur-doped GQDs exhibit pH-dependent fluorescence response that is successfully utilized as a sensing mechanism for acidic extracellular environments of cancer cells It allows for the deterministic, ratiometric spectral discrimination between cancerous (HeLa and MCF-7 cell) versus healthy (HEK-293 cell) environments with substantial intensity ratios of 16 to 8 These results suggest fully biocompatible GQDs developed in this work as multifunctional candidates for in vitro delivery of active agents, multicolor visible/near-IR fluorescence imaging, and pH-sensing of cancerous environments

Doped Graphene Quantum Dots for Intracellular Multicolor Imaging and Cancer Detection.

The impact of mesoporous silicon (PSi) particles—embedded either on the surface, or totally encapsulated within electrospun poly (e-caprolactone) (PCL) fibers—on its properties as a tissue engineering scaffold is assessed. Our findings suggest that the resorbable porous silicon component can sensitively accelerate the necessary calcification process in such composites. Calcium phosphate deposition on the scaffolds was measured via in vitro calcification assays both at acellular and cellular levels. Extensive attachment of fibroblasts, human adult mesenchymal stem cells, and mouse stromal cells to the scaffold were observed. Complementary cell differentiation assays and ultrastructural measurements were also carried out; the levels of alkaline phosphatase expression, a specific biomarker for mesenchymal stem cell differentiation, show that the scaffolds have the ability to mediate such processes, and that the location of the Si plays a key role in levels of expression.

Giridhar R. Akkaraju

Papers

Porous silicon-based scaffolds for tissue engineering and other biomedical applications

Graphene Oxide as a Multifunctional Platform for Intracellular Delivery, Imaging, and Cancer Sensing.

High-Porosity Poly(ε-Caprolactone)/Mesoporous Silicon Scaffolds: Calcium Phosphate Deposition and Biological Response to Bone Precursor Cells

Doped Graphene Quantum Dots for Intracellular Multicolor Imaging and Cancer Detection.

The role of nanostructured mesoporous silicon in discriminating in vitro calcification for electrospun composite tissue engineering scaffolds