Cellular Deformations Induced by Conical Silicon Nanowire Arrays Facilitate Gene Delivery

Engineered cell–nanostructured interfaces generated by vertically aligned silicon nanowire (SiNW) arrays have become a promising platform for orchestrating cell behavior, function, and fate. However, the underlying mechanism in SiNW-mediated intracellular access and delivery is still poorly understood. This study demonstrates the development of a gene delivery platform based on conical SiNW arrays for mechanical cell transfection, assisted by centrifugal force, for both adherent and nonadherent cells in vitro. Cells form focal adhesions on SiNWs within 6 h, and maintain high viability and motility. Such a functional and dynamic cell–SiNW interface features conformational changes in the plasma membrane and in some cases the nucleus, promoting both direct penetration and endocytosis; this synergistically facilitates SiNW-mediated delivery of nucleic acids into immortalized cell lines, and into difficult-to-transfect primary immune T cells without pre-activation. Moreover, transfected cells retrieved from SiNWs retain the capacity to proliferate—crucial to future biomedical applications. The results indicate that SiNW-mediated intracellular delivery holds great promise for developing increasingly sophisticated investigative and therapeutic tools. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.</p

The Essential Elements of a Risk Governance Framework for Current and Future Nanotechnologies

Societies worldwide are investing considerable resources into the safe development and use of nanomaterials. Although each of these protective efforts is crucial for governing the risks of nanomaterials, they are insufficient in isolation. What is missing is a more integrative governance approach that goes beyond legislation. Development of this approach must b

Silicon diatom frustules as nanostructured photoelectrodes

In the quest for solutions to meeting future energy demands, solar fuels play an important role. A particularly promising example is photocatalysis since even incremental improvements in performance in this process are bound to translate into significant cost benefits. Here, we report that semiconducting and high surface area 3D silicon replicas prepared from abundantly available diatom fossils sustain photocurrents and enable solar energy conversion.Soundarrajan Chandrasekaran, Martin J. Sweetman, Krishna Kant, William Skinner, Dusan Losic, Thomas Nann and Nicolas H. Voelcke

High-throughput assessment and modeling of a polymer library regulating human dental pulp-derived stem cell behavior

The identification of biomaterials that modulate cell responses is a crucial task for tissue engineering and cell therapy. The identification of novel materials is complicated by the immense number of synthesizable polymers and the time required for testing each material experimentally. In the current study, polymeric biomaterial-cell interactions were assessed rapidly using a microarray format. The attachment, proliferation, and differentiation of human dental pulp stem cells (hDPSCs) were investigated on 141 homopolymers and 400 diverse copolymers. The copolymer of isooctyl acrylate and 2-(methacryloyloxy)ethyl acetoacetate achieved the highest attachment and proliferation of hDPSC, whereas high cell attachment and differentiation of hDPSC were observed on the copolymer of isooctyl acrylate and trimethylolpropane ethoxylate triacrylate. Computational models were generated, relating polymer properties to cellular responses. These models could accurately predict cell behavior for up to 95% of materials within a test set. The models identified several functional groups as being important for supporting specific cell responses. In particular, oxygen-containing chemical moieties, including fragments from the acrylate/acrylamide backbone of the polymers, promoted cell attachment. Small hydrocarbon fragments originating from polymer pendant groups promoted cell proliferation and differentiation. These computational models constitute a key tool to direct the discovery of novel materials within the enormous chemical space available to researchers.Soraya Rasi Ghaemi, Bahman Delalat, Stan Gronthos, Morgan R. Alexander, David A. Winkler, Andrew L. Hook, and Nicolas H. Voelcke

Maximizing RNA loading for gene silencing using porous silicon nanoparticles

Gene silencing by RNA interference is a powerful technology with broad applications. However, this technology has been hampered by the instability of small interfering RNA (siRNA) molecules in physiological conditions and their inefficient delivery into the cytoplasm of target cells. Porous silicon nanoparticles have emerged as a potential delivery vehicle to overcome these limitations-being able to encapsulate RNA molecules within the porous matrix and protect them from degradation. Here, key variables were investigated that influence siRNA loading into porous silicon nanoparticles. The effect of modifying the surface of porous silicon nanoparticles with various amino-functional molecules as well as the effects of salt and chaotropic agents in facilitating siRNA loading was examined. Maximum siRNA loading of 413 μg/(mg of porous silicon nanoparticles) was found when the nanoparticles were modified by a fourth generation polyamidoamine dendrimer. Low concentrations of urea or salt increased loading capacity: an increase in RNA loading by 19% at a concentration of 0.05 M NaCl or 21% at a concentration of 0.25 M urea was observed when compared to loading in water. Lastly, it was demonstrated that dendrimer-functionalized nanocarriers are able to deliver siRNA against ELOVL5, a target for the treatment of advanced prostate cancer.Terence Tieu, Sameer Dhawan, V. Haridas, Lisa M. Butler, Helmut Thissen, Anna Cifuentes-Rius, Nicolas H. Voelcke

Real-time detection of per-fluoroalkyl substance (PFAS) self-assembled monolayers in nanoporous interferometers

Identification and quantification of per- and polyfluoroalkyl substances (PFASs) remain challenging due to their chemical diversity, and their inert optical and chemical nature. Here, we present an optical system integrating perfluorosilane-functionalized nanoporous anodic alumina (NAA) interferometers with reflectometric interference spectroscopy (RIfS) for real-time, label-free detection of self-assembled monolayers (SAMs) of perfluorooctanoic acid (PFOA) as a model PFAS. Measured changes in the effective optical thickness (ΔOT(eff)) of NAA interferometers made it possible to study the fluorous interaction-induced self-assembly of PFOA molecules with perfluorosilane functional molecules of varying length, in real time and in situ. Analysis of key sensing parameters—sensitivity, low limit of detection and linearity—allowed us to determine the most optimal molecular length of perfluorosilanes to maximize immobilization of PFOA onto functional surfaces. Freundlich and Langmuir isotherm models were adapted to experimentally acquired values of ΔOT(eff) to elucidate the mechanism of PFOA–perfluorosilane interactions. Interpretation of these models suggests that PFOA binds to perfluorosilanes functional groups immobilized onto the inner surface of NAA interferometers through a fluorous interaction-induced Freundlich mechanism. The potential real-life applicability of this system was demonstrated by detecting the formation of PFOA-based SAMs in aqueous matrices of varying complexity (i.e. ultrapure, deionized, tap, and river water). This study provides new insights into how functional surface chemistries can be engineered to maximize sensitivity and selectivity to PFAS, harnessing fluorous interactions—with implications for future deployable systems to detect and remove these emerging toxicants.Cheryl Suwen Law, Juan Wang, Satyathiran Gunenthiran, Siew Yee Lim, Andrew D. Abell, Lutz Ahrens, Tushar Kumeria, Abel Santos, Nicolas H. Voelcke

Patient-derived prostate cancer explants: a clinically relevant model to assess siRNA-based nanomedicines

Over the last thirty years, research in nanomedicine has widely been focused on applications in cancer therapeutics. However, despite the plethora of reported nanoscale drug delivery systems that can successfully eradicate solid tumor xenografts in vivo, many of these formulations have not yet achieved clinical translation. This issue particularly pertains to the delivery of small interfering RNA (siRNA), a highly attractive tool for selective gene targeting. One of the likely reasons behind the lack of translation is that current in vivo models fail to recapitulate critical elements of clinical solid tumors that may influence drug response, such as cellular heterogeneity in the tumor microenvironment. This study incorporates a more clinically relevant model for assessing siRNA delivery systems; ex vivo culture of prostate cancer harvested from patients who have undergone radical prostatectomy, denoted patient-derived explants (PDE). The model retains native human tissue architecture, microenvironment, and cell signaling pathways. Porous silicon nanoparticles (pSiNPs) behavior in this model is investigated and compared with commonly used 3D cancer cell spheroids for their efficacy in the delivery of siRNA directed against the androgen receptor (AR), a key driver of prostate cancer.Terence Tieu, Swati Irani, Kayla L. Bremert, Natalie K. Ryan, Marcin Wojnilowicz, Madison Helm, Helmut Thissen, Nicolas H. Voelcker, Lisa M. Butler, and Anna Cifuentes-Riu

Tailor-engineered plasmonic single-lattices: harnessing localized surface plasmon resonances for visible-NIR light-enhanced photocatalysis

A platform material composed of 2D gold (Au) nanodot plasmonic single-lattices (Au-nD-PSLs) featuring tailor-engineered geometric features for visible-NIR light-driven enhanced photocatalysis is presented. Au-nD-PSLs efficiently harness incident visible-NIR electromagnetic waves to accelerate photo-chemical reactions by localized surface plasmon resonance (LSPR) effects. Au-nD-PSLs are fabricated by a straightforward, industrially scalable template-assisted approach, using nanopatterned aluminum substrates as templates. The method overcomes the constraints of direct writing lithography and allows Au-nD-PSLs to be transferred to arbitrary functional flexible substrates. Triangular lattice Au-nD-PSLs feature tunable and controllable characteristic LSPR bands across the visible spectrum. Strongly localized electromagnetic fields around Au-nD-PSLs are responsible for the outstanding photocatalytic performance of these plasmonic nanostructures, as demonstrated by finite-difference time-domain simulations and experimental observations. Our approach of rational engineering of LSPR effects in Au-nD-PSLs provides exciting opportunities to develop high-performing and reusable photocatalysts that harvest the visible-NIR spectrum for a broad range of optoelectronic and plasmonic applications.Siew Yee Lim, Cheryl Suwen Law, Francesc Bertó-Roselló, Lina Liu, Marijana Markovic, Josep Ferré-Borrull, Andrew D. Abell, Nicolas H. Voelcker, Lluís F. Marsal and Abel Santo