Repair spinal cord injury with a versatile anti-oxidant and neural regenerative nanoplatform.

Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.

Molecular interaction of quercetin and its derivatives against nucleolin in breast cancer: in-silico and in-vitro study.

Nucleolin, a multifaceted RNA binding domain protein is overexpressed in various cancers leading to dysfunction of several cellular signaling pathways. Quercetin, a distinctive bioactive molecule, along with its derivatives have shown exclusive physio-chemical properties which makes them appealing choices for drug development, yet their role in targeted cancer therapy is limited. Here, the RBD domain structure of Nucleolin was modeled and stabilized by MD simulations for a period of 1000 ns. Molecular docking was performed to determine the binding capability of ligands with the target. To determine the stability of the ligand inside the binding pocket of the protein, MD simulation was performed for a period of 250 ns each for Quercetin-4'-o'-Glucoside, Quercetin_9 and Quercetin complexes. Further, in-vitro studies including cytotoxicity and RT-PCR assays were performed to validate quercetin against Nucleolin. Molecular docking and MD Simulation studies suggested a potential mechanism of interaction of Quercetin-4'-o'-Glucoside, Querectin_9 and Quercetin with Nucleolin with the binding free energy of -63.653, -58.86 and -46.9 kcal/mol, respectively. Moreover, Lys 348 and Glu379 were identified as important amino acids in ligand interaction located at the RRM2 motif of Nucleolin. In-vitro studies showed significant downregulation in Nucleolin expression by 15.18 and 2.51-fold at 48h and 72h respectively in MCF-7 cells with Quercetin (IC50 = 160 µM). Our findings suggested the potential role of specific RRM motifs in interaction with natural compounds targeting Nucleolin. This could be an effective strategy in the identification of potential molecules in targeting Nucleolin which can be further explored for developing targeted therapies for breast cancer.Communicated by Ramaswamy H. Sarma.

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models.

BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

Virus-like silica nanoparticles enhance macromolecule permeation in vivo.

Nanoparticle based permeation enhancers have the potential to improve the oral delivery of biologics. Recently, solid silica nanoparticles were discovered to improve the intestinal permeability of peptides and proteins via transient opening of the gut epithelium. In this study, we have developed small-sized (∼60 nm) virus-like silica nanoparticles (VSNP) as a reversible and next generation non-toxic permeation enhancer for oral delivery of biologics. Our results show that the anionic VSNP showed a better permeation-enhancing effect than the same sized spherical Stöber silica nanoparticles (∼60 nm) by enhancing the apparent insulin permeability by 1.3-fold in the Caco-2 monolayer model and by 1.2-fold in the Caco-2/MTX-HT-29 co-culture model. In vivo experiments in healthy mice demonstrated that anionic VSNP significantly enhanced the permeation of fluorescently labelled 4 kDa dextran after oral administration compared to Stöber nanoparticles and positively charged VSNP. The results indicated that the nanoscale surface roughness is an important consideration when designing nanoparticle-based permeation enhancers. Overall, our study shows for the first time that small-sized (∼60 nm) VSNP with nanoscale surface roughness can be used as a non-toxic permeation enhancer for oral delivery of therapeutic peptides and proteins.

Adsorption of Magenta Dye on PbO Doped MgZnO: Interpretation of Statistical Physics Parameters Using Double-Layer Models.

This article reports the synthesis of PbO doped MgZnO (PbO@MgZnO) by a co-precipitation method, followed by an ultrasonication process. PbO@MgZnO demonstrates a significant adsorption capability toward Magenta Dye (MD). The greatest adsorption capability was optimized by varying parameters such as pH, MD concentration, and adsorbent dose. The kinetics study illustrates that the adsorption of MD on PbO@MgZnO follows the pseudo-second-order. The isotherm study revealed that Langmuir is best fitted for the adsorption, but with little difference in the R2 value of Langmuir and Freundlich, the adsorption process cloud be single or multi-layer. The maximum adsorption capacity was found to be 333.33 mg/g. The negative ΔG refers to the spontaneity of MD adsorption on PbO@MgZnO. The steric parameters from statistical physics models also favor the multi-layer adsorption mechanism. As a function of solution temperature, the parameter n pattern has values of n = 0.395, 0.290, and 0.280 for 298, 308, and 318 K, respectively (i.e., all values were below 1). Therefore, horizontal molecule positioning and multiple locking mechanisms were implicated during interactions between MD and PbO@MgZnO active sites.

Sustained release ketamine-loaded porous silicon-PLGA microparticles prepared by an optimized supercritical CO2 process.

Ketamine in sub-anaesthetic doses has analgesic properties and an opioid-sparing effect. Intrathecal (i.t.) delivery of analgesics bypasses systemic metabolism and delivers the analgesic agent adjacent to the target receptors in the spinal cord and so small doses are required to achieve effective pain relief. In order to relieve intractable cancer-related pain, sustained-release ketamine formulations are required in combination with a strong opioid because frequent i.t. injection is not practical. In this study, ketamine or ketamine-loaded porous silicon (pSi) were encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles by a novel supercritical carbon dioxide (scCO2) method, thereby avoiding the use of organic solvent. Multiple parameters including theoretical drug loading (DL), presence of pSi, size of scCO2 vessel, PLGA type, and use of co-solvent were investigated with a view to obtaining high DL and a sustained-release for an extended period. The most important finding was that the use of a large scCO2 vessel (60 mL) resulted in a much higher encapsulation efficiency (EE) compared with a small vessel (12 mL). In addition, pre-loading ketamine into pSi slightly improved the level of drug incorporation (i.e. EE and DL). Although the in vitro release was mainly affected by the drug payload, the use of the large scCO2 vessel reduced the burst release and extended the release period for PLGA microparticles with 10% or 20% ketamine loading. Together, our findings provide valuable information for optimization of drug delivery systems prepared with the aid of scCO2.

Frontiers in the treatment of glioblastoma: Past, present and emerging.

Glioblastoma (GBM) is one of the most aggressive cancers of the brain. Despite extensive research over the last several decades, the survival rates for GBM have not improved and prognosis remains poor. To date, only a few therapies are approved for the treatment of GBM with the main reasons being: 1) significant tumour heterogeneity which promotes the selection of resistant subpopulations 2) GBM induced immunosuppression and 3) fortified location of the tumour in the brain which hinders the delivery of therapeutics. Existing therapies for GBM such as radiotherapy, surgery and chemotherapy have been unable to reach the clinical efficacy necessary to prolong patient survival more than a few months. This comprehensive review evaluates the current and emerging therapies including those in clinical trials that may potentially improve both targeted delivery of therapeutics directly to the tumour site and the development of agents that may specifically target GBM. Particular focus has also been given to emerging delivery technologies such as focused ultrasound, cellular delivery systems nanomedicines and immunotherapy. Finally, we discuss the importance of developing novel materials for improved delivery efficacy of nanoparticles and therapeutics to reduce the suffering of GBM patients.

Moldless Printing of Silicone Lenses With Embedded Nanostructured Optical Filters.

Optical lenses are among the oldest technological innovations (3000 years ago) and they have enabled a multitude of applications in healthcare and in our daily lives. The primary function of optical lenses has changed little over time; they serve mainly as a light-collection (e.g. reflected, transmitted, diffracted) element, and the wavelength and/or intensity of the collected light is usually manipulated by coupling with various external optical filter elements or coatings. This generally results in losses associated with multiple interfacial reflections, and increases the complexity of design and construction. In this work we introduce a change in this paradigm, by integrating both light-shaping and image magnification into a single lens element using a moldless procedure that takes advantage of the physical and optical properties of mesoporous silicon (PSi) photonic crystal nanostructures. Casting of a liquid poly(dimethyl) siloxane (PDMS) pre-polymer solution onto a PSi film generates a droplet with contact angle that is readily controlled by the silicon nanostructure, and adhesion of the cured polymer to the PSi photonic crystal allows preparation of lightweight (10 mg) freestanding lenses (4.7 mm focal length) with an embedded optical component (e.g. optical rugate filter, resonant cavity, distributed Bragg reflector). Our fabrication process shows excellent reliability (yield 95%) and low cost and we expect our lens to have implications in a wide range of applications. As a proof-of-concept, using a single monolithic lens/filter element we demonstrate: fluorescence imaging of isolated human cancer cells with rejection of the blue excitation light, through a lens that is self-adhered to a commercial smartphone; shaping the emission spectrum of a white light emitting diode (LED) to tune the color from red through blue; and selection of a narrow wavelength band (bandwidth 5 nm) from a fluorescent molecular probe.

Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy.

Resveratrol (RES) is a naturally existing polyphenol which exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties. In recent years, RES has attracted attention for its synergistic effect with other anti-cancer drugs for the treatment of drug resistant cancers. However, RES faces the issues of poor pharmacokinetics, stability and low solubility which limits its clinical application. In present study, RES has been loaded onto uniformly sized (~60 nm) mesoporous silica nanoparticles (MSNs) to improve its in vitro anti-proliferative activity and sensitization of Docatexal in hypoxia induced drug resistance in prostate cancer. RES was efficiently encapsulated within phosphonate (negatively charged) and amine (positively charged) modified MSNs. The effect of surface functionalization was studied on the loading, in vitro release, anti-proliferative and cytotoxic potential of RES using prostate cancer cell line. At pH 7.4 both free and NH2-MSNs loaded RES showed burst release which was plateaued with almost 90% of drug released in first 12 h. On the other hand, PO3-MSNs showed significantly slower release kinetics with only 50% drug release in first 12 h at pH 7.4. At pH 5.5, however, both the PO3-MSNs and NH2-MSNs showed significant control over release (around 40% less release compared with free RES in 24 h). Phosphonate modified MSNs significantly enhanced the anti-proliferative potential of RES with an IC50 of 7.15 µM as compared to 14.86 µM of free RES whereas amine modified MSNs didn't affect proliferation with an IC50 value higher than free RES (20.45 µM). Furthermore, RES loaded onto PO3-MSNs showed robust and dose dependent sensitization of Docatexal in hypoxic cell environment which was comparable to pure RES solution. This study provides an example of applicability of MSNs loaded with polyphenols such as RES as next generation anticancer formulations for treating drug resistant cancers such as prostate cancer.

Enhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles.

Suberoylanilide hydroxamic acid (SAHA) or vorinostat (VOR) is a potent inhibitor of class I histone deacetylases (HDACs) that is approved for the treatment of cutaneous T-cell lymphoma. However, it has the intrinsic limitations of low water solubility and low permeability which reduces its clinical potential especially when given orally. Packaging of drugs within ordered mesoporous silica nanoparticles (MSNs) is an emerging strategy for increasing drug solubility and permeability of BCS (Biopharmaceutical Classification System) class II and IV drugs. In this study, we encapsulated vorinostat within MSNs modified with different functional groups, and assessed its solubility, permeability and anti-cancer efficacy in vitro. Compared to free drug, the solubility of vorinostat was enhanced 2.6-fold upon encapsulation in pristine MSNs (MCM-41-VOR). Solubility was further enhanced when MSNs were modified with silanes having amino (3.9 fold) or phosphonate (4.3 fold) terminal functional groups. Moreover, permeability of vorinostat into Caco-2 human colon cancer cells was significantly enhanced for MSN-based formulations, particularly MSNs modified with amino functional group (MCM-41-NH2-VOR) where it was enhanced ~4 fold. Compared to free drug, vorinostat encapsulated within amino-modified MSNs robustly induced histone hyperacetylation and expression of established histone deacetylase inhibitor (HDACi)-target genes, and induced extensive apoptosis in HCT116 colon cancer cells. Similar effects were observed on apoptosis induction in HH cutaneous T-cell lymphoma cells. Thus, encapsulation of the BCS class IV molecule vorinostat within MSNs represents an effective strategy for improving its solubility, permeability and anti-tumour activity.

Multifunctional microspherical magnetic and pH responsive carriers for combination anticancer therapy engineered by droplet-based microfluidics.

pH stimuli responsive drug delivery platforms that can target specific locations along the gastrointestinal tract hold great promise for colorectal cancer therapy. Herein, we present a facile approach to produce microfluidic engineered pH-sensitive magnetic microspherical carriers containing multifunctional therapeutic payloads for synergistic treatment of colorectal cancer. Chemotherapeutics, 5 fluorouracil (5FU) and curcumin (CUR), were chosen due to their synergistic effect for colorectal cancer treatment and prevention. Drugs were loaded onto naturally derived porous silicon nanoparticles (SiNPs) and magnetic bacterial iron oxide nanowires (BacNWs), which acted as drug nanocontainers and magnetic elements, respectively. Drug loaded SiNPs and BacNWs were then encapsulated into polymeric microspheres using droplet-based microfluidics. To ensure controlled drug delivery into the desired site of action (colon and rectum), the microspheres were fabricated using hypromellose acetate succinate polymers, which are insoluble in the acidic medium of the stomach (i.e. pH 1.2) but soluble at basic pH (colon and rectum). Our results confirmed that the microspheres exhibit a narrow size distribution (CV > 5%) with precise size control. Moreover, in vitro dissolution and drug release data confirmed their pH-responsive properties. Motivated by these results, we explored the biocompatibility of microspheres using human RAW 264.7 macrophages. The results revealed the safety of drug free microspheres up to 1000 µg mL-1. Finally, the synergistic action of 5FU and CUR loaded microspheres was investigated on SW480 colon adenocarcinoma cells.

From The Mine to Cancer Therapy: Natural and Biodegradable Theranostic Silicon Nanocarriers from Diatoms for Sustained Delivery of Chemotherapeutics.

Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages. In this paper, a new mesoporous biodegradable silicon nanoparticle (SiNP) drug carrier obtained from natural diatom silica mineral available from the mining industry is presented. Diatom silica structures are mechanically fragmented and converted into SiNPs by simple and scalable magnesiothermic reduction process. Results show that SiNPs have many desirable properties including high surface area, high drug loading capacity, strong luminescence, biodegradability, and no cytotoxicity. The in-vitro release results from SiNPs loaded with anticancer drugs (doxorubicin) demonstrate a pH-dependent and sustained drug release with enhanced cytotoxicity against cancer cells. The cells study using doxorubicin loaded SiNPs shows a significantly enhanced cytotoxicity against cancer cells compared with free drug, suggesting their considerable potential as theranostic nanocarriers for chemotherapy. Their low-cost manufacturing using abundant natural materials and outstanding chemotherapeutic performance has made them as a promising alternative to synthetic nanoparticles for drug delivery applications.

Naturally Derived Iron Oxide Nanowires from Bacteria for Magnetically Triggered Drug Release and Cancer Hyperthermia in 2D and 3D Culture Environments: Bacteria Biofilm to Potent Cancer Therapeutic.

Iron oxide nanowires produced by bacteria (Mariprofundus ferrooxydans) are demonstrated as new multifunctional drug carriers for triggered therapeutics release and cancer hyperthmia applications. Iron oxide nanowires are obtained from biofilm waste in the bore system used to pump saline groundwater into the River Murray, South Australia (Australia) and processed into individual nanowires with extensive magnetic properties. The drug carrier capabilities of these iron oxide nanowires (Bac-FeOxNWs) are assessed by loading anticancer drug (doxorubicin, Dox) followed by measuring its elution under sustained and triggered release conditions using alternating magnetic field (AMF). The cytotoxicity of Bac-FeOxNWs assessed in 2D (96 well plate) and 3D (Matrigel) cell cultures using MDA-MB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells shows that these Bac-FeOxNWs are biocompatible even at concentrations as high as 250 µg/mL after 24 h of incubation. Finally, we demonstrate the capabilities of Bac-FeOxNWs as potential hyperthermia agent in 3D culture setup. Application of AMF increased the local temperature by 14 °C resulting in approximately 34% decrease in cell viability. Our results demonstrate that these naturally produced nanowires in the form of biofilm can efficiently act as drug carriers with triggered payload release and magnetothermal heating features for potential anticancer therapeutics applications.

Iron Oxide Nanowires from Bacteria Biofilm as an Efficient Visible-Light Magnetic Photocatalyst.

Naturally produced iron oxide nanowires by Mariprofundus ferrooxydans bacteria as biofilm are evaluated for their structural, chemical, and photocatalytic performance under visible-light irradiation. The crystal phase structure of this unique natural material presents a 1-dimensional (1D) nanowire-like geometry, which is transformed from amorphous to crystalline (hematite) by thermal annealing at high temperature without changing their morphology. This study systematically assesses the effect of different annealing temperatures on the photocatalytic activity of iron oxide nanowires produced by Mariprofundus ferrooxydans bacteria. The nanowires processed at 800 °C were the most optimal for photocatalytic applications degrading a model dye (rhodamine B) in less than an hour. These nanowires displayed excellent reusability with no significant loss of activity even after 6 cycles. Kinetic studies by using hydrogen peroxide (radical generator) and isopropyl alcohol (radical scavenger) suggest that OH• is the dominant photooxidant. These nanowires are naturally produced, inexpensive, highly active, stable, and magnetic and have the potential to be used for broad applications including environmental remediation, water disinfection, and industrial catalysis.

Advanced biopolymer-coated drug-releasing titania nanotubes (TNTs) implants with simultaneously enhanced osteoblast adhesion and antibacterial properties.

Here, we report on the development of advanced biopolymer-coated drug-releasing implants based on titanium (Ti) featuring titania nanotubes (TNTs) on its surface. These TNT arrays were fabricated on the Ti surface by electrochemical anodization, followed by the loading and release of a model antibiotic drug, gentamicin. The osteoblastic adhesion and antibacterial properties of these TNT-Ti samples are significantly improved by loading antibacterial payloads inside the nanotubes and modifying their surface with two biopolymer coatings (PLGA and chitosan). The improved osteoblast adhesion and antibacterial properties of these drug-releasing TNT-Ti samples are confirmed by the adhesion and proliferation studies of osteoblasts and model Gram-positive bacteria (Staphylococcus epidermidis). The adhesion of these cells on TNT-Ti samples is monitored by fluorescence and scanning electron microscopies. Results reveal the ability of these biopolymer-coated drug-releasing TNT-Ti substrates to promote osteoblast adhesion and proliferation, while effectively preventing bacterial colonization by impeding their proliferation and biofilm formation. The proposed approach could overcome inherent problems associated with bacterial infections on Ti-based implants, simultaneously enabling the development of orthopedic implants with enhanced and synergistic antibacterial functionalities and bone cell promotion.

Engineered therapeutic-releasing nanoporous anodic alumina-aluminum wires with extended release of therapeutics.

In this study, we present a nanoengineered therapeutic-releasing system based on aluminum wires featuring nanoporous anodic alumina layers and chitosan coatings. Nanoporous anodic alumina layers are produced on the surface of aluminum wires by electrochemical anodization. These nanoporous layers with precisely engineered nanopore geometry are used as nanocontainers for bovine serum albumin molecules labeled with fluorescein isothiocyanate (BSA-FITC), which is selected as a model drug. The surface of these therapeutic-releasing implants is coated with a biocompatible and biodegradable polymer, chitosan, in order to achieve a sustained release of protein over extended periods of time. The performance of this therapeutic-releasing device is systematically assessed through a series of experiments under static and dynamic flow conditions. In these experiments, the effect of such parameters as the number of layers of chitosan coating and the temperature and pH of the eluting medium is established. The obtained results reveal that the proposed therapeutic-releasing system based on nanoporous aluminum wires can be engineered with sustained release performance for up to 6.5 weeks, which is a critical factor for medical treatments using sensitive therapeutics such as proteins and genes when a localized delivery is desired.

Localized drug delivery of selenium (Se) using nanoporous anodic aluminium oxide for bone implants.

Electrochemically engineered nanoporous anodized aluminium oxide (AAO) prepared on aluminium (Al) foil by anodization process was employed as a platform for loading different forms of selenium (Se) in order to investigate their release behaviour and potential application for localized drug delivery targeting bone cancer. Several forms of Se including inorganic Se (H2SeO3), organic Se ((C6H5)2Se2), metallic Se, their chitosan composites, electrodeposited (ED) and chemical vapour deposited (CVD) Se were explored and combined with another model drug (indomethacin). Structural, drug-loading and in vitro drug-releasing characteristics of prepared Se-based drug delivery carriers were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and UV-visible spectroscopy (UV-Vis), respectively. Sustained and controlled release of Se was demonstrated through chitosan-composites of inorganic, organic or metallic forms of Se loaded into nanoporous AAO carriers. Cell viability studies showed decreasing toxicity to cancer cells in the order: inorganic Se > ED Se > CVD Se > metallic Se > organic Se. The study suggests new alternatives for localized drug treatment based on low-cost nano-engineered carriers loaded with Se having anti-cancer properties.

Optically optimized photoluminescent and interferometric biosensors based on nanoporous anodic alumina: a comparison.

Herein, we present a comparative study about the sensing performance of optical biosensors based on photoluminescence spectroscopy (PLS) and reflectometric interference spectroscopy (RIfS) combined with nanoporous anodic alumina (NAA) platforms when detecting different analytes under distinct adsorption conditions. First, NAA platforms are structurally engineered in order for optimizing the optical signals obtained by PLS and RIfS. Then, the most optimal NAA platforms combined with PLS and RIfS are quantitatively compared by detecting two different analytes: d-glucose and l-cysteine under nonspecific and specific adsorption conditions, respectively. The obtained results demonstrate that such parameters as the analyte nature and adsorption conditions play a direct role in the sensing performance of these platforms. However, as this study demonstrates, PLS-NAA platforms are more sensitive than RIfS-NAA ones. The former shows better linearity (i.e., proportional change in the sensing parameter with analyte concentration), higher sensitivity toward analytes (i.e., sharper change in the sensing parameter with analyte concentration), and lower limit of detection (i.e., minimum detectable concentration of analyte).

Label-free reflectometric interference microchip biosensor based on nanoporous alumina for detection of circulating tumour cells.

In this report, a label-free reflectometric interference spectroscopy (RIfS) based microchip biosensor for the detection of circulating tumour cells (CTCs) is demonstrated. Highly ordered nanoporous anodic aluminium oxide (AAO) fabricated by electrochemical anodization of aluminium foil was used as the RIfS sensing platform. Biotinylated anti-EpCAM antibody that specifically binds to human cancer cells of epithelial origin such as pancreatic cancer cells (PANC-1) was covalently attached to the AAO surface through multiple surface functionalization steps. Whole blood or phosphate buffer saline spiked with low numbers of pancreatic cancer cells were successfully detected by specially designed microfluidic device incorporating an AAO RIfS sensor, without labour intensive fluorescence labelling and/or pre-enhancement process. Our results show that the developed device is capable of selectively detecting of cancer cells, within a concentrations range of 1000-100,000 cells/mL, with a detection limit of <1000 cells/mL, a response time of <5 min and sample volume of 50 µL of. The presented RIfS method shows considerable promise for translation to a rapid and cost-effective point-of-care diagnostic device for the detection of CTCs in patients with metastatic cancer.