Facile preparation of a cost-effective platform based on ZnFe2O4 nanomaterials for electrochemical cell detection.

Circulating tumor cells (CTCs) are important tumor markers that indicate early metastasis, tumor recurrence, and treatment efficacy. To identify and separate these cells from the blood, new nanomaterials need to be developed. The present study explored the potential application of ZnFe2O4 magnetic nanoparticles in capturing CTCs with cell surface markers. Folic acid was coupled to L-cysteine-capped ZnFe2O4 nanoparticles (ZC) to provide binding sites on ZnFe2O4 nanoparticles for the recognition of folate bioreceptors, which are highly expressed in MCF-7 breast cancer cells. The cytotoxicity of ZnFe2O4 nanoparticles and ZC against MCF-7 was analyzed with the MTT assay. After 24 h of incubation, there were IC50 values of 702.6 and 805.5 µg/mL for ZnFe2O4 and ZC, respectively. However, after 48 h of incubation, IC50 values of ZnFe2O4 and ZC were reduced to 267.3 and 389.7 µg/mL, respectively. The cell quantification was conducted with magnetically collected cells placed on a glassy carbon electrode, and the differential pulse voltammetry (DPV) responses were analyzed. This cost-effective ZnFe2O4-based biosensing platform allowed cancer cell detection with a limit of detection of 3 cells/mL, ranging from 25 to 104 cells/mL. In future, these functionalized zinc ferrites may be used in electrochemical cell detection and targeted cancer therapy.

Hierarchal polyaniline-folic acid nanostructures act as a platform for electrochemical detection of tumor cells.

The fabrication of electrochemical sensing platforms for cancer monitoring by quantifying circulating tumor cells (CTCs) in blood holds promise for providing a low-cost, rapid, feasible, and safe approach for cancer diagnosis. Here, we isolate cancer cells using CoFe2O4 nanoparticles functionalized with folic acid and chitosan as an inexpensive magnetic nanoprobe. This electrochemical cytosensing platform was realized using polyaniline-folic acid nanohybrids with a three-dimensional hierarchical structure that presents abundant affinity sites toward overexpressed folate bioreceptors on cancer cells, in addition to retaining satisfied conductivity. Furthermore, 3D modeling and simulation of the polyaniline-folic acid structures were conducted to investigate the stable complex between aniline and folate, and the interaction between the polyaniline-folate complex and folate receptor alpha1, a bioreceptor on MCF-7 was revealed for the first time. The limit of detection was calculated to be 4 cells mL-1 with a linear range from 50 to 106 cells mL-1.

Glutaraldehyde crosslinked doxorubicin promotes drug delivery efficiency using cobalt ferrite nanoparticles.

Doxorubicin (DOX) is a common chemotherapy agent that is used in clinics for the treatment of a wide spectrum of cancers. Herein, a novel approach for improving doxorubicin loading on nanoparticles and also controlled release is suggested using crosslinking doxorubicin molecules with glutaraldehyde. We investigated the loading efficiency of doxorubicin on CoFe2O4 nanoparticles in the absence and presence of glutaraldehyde. Based on the feasible, one-pot, and time-saving approach suggested here, the crosslinked DOX showed loading efficiency about twice more in comparison with the non-crosslinked DOX. In vitro doxorubicin release of three formulations including DOX crosslinked with glutaraldehyde (DOXGA), DOX loaded on CoFe2O4 (CFDOX) and DOX loaded on CoFe2O4 using glutaraldehyde (CFDOXGA) yielded a sustained release. The kinetic models such as first-order, Sahlin-Peppas, and Higuchi were employed for further exploration of DOX release profile. Our suggested method might extend to other nanomaterial-based drug delivery formulations to promote drug delivery efficiency.

Optical cytosensors for the detection of circulating tumour cells.

Blood analysis is an established approach to monitor various diseases, ranging from heart defects and diabetes to cancer. Among various tumor markers in the blood, circulating tumor cells (CTCs) have received increasing attention due to the fact that they originate directly from the tumors. Capturing and detecting CTCs represents a promising approach in cancer diagnostics and clinical management of cancers. CTCs in blood progress to self-seeding a tumour or initiating a new lesion mass. Cytosensors are biosensors intended to identify CTCs in a blood sample of cancer patients and provide information about the cancer status. Herein, we firstly discuss different detection methods of state-of-the-art optical cytosensors, including colorimetry, fluorescence, surface plasmon resonance, photoelectrochemistry and electrochemiluminescence. Then we review the significant advances made in implementing biorecognition elements and nanomaterials for the detection of cancer cells. Despite great progress in optical cytosensors, and their integration with smartphones, they have still only been explored to prototype stages. Much more effort is needed to fulfil their potential in modern cancer diagnostics and in monitoring the state of disease for cancer patients.

MXene-based cytosensor for the detection of HER2-positive cancer cells using CoFe2O4@Ag magnetic nanohybrids conjugated to the HB5 aptamer.

MXenes are a new class of conductive two-dimensional material which have received growing attention in biosensing for their significant surface area and unique surface chemistry. Here, gold electrodes were modified with MXene nanosheets of about 2 nm thickness and 1.5 µm lateral size for the electrochemical detection of tumor cells. An HB5 aptamer with high selectivity for HER-2 positive cells was immobilized on the MXene layers via electrostatic interactions. To minimize electrode biofouling with blood matrix, magnetic separation of HER-2 positive circulating tumor cells was carried out using CoFe2O4@Ag magnetic nanohybrids bonded to the HB5. The formation of sandwich-like structures between the magnetically captured cells and the functionalized MXene electrodes effectively shields the electron transfer of a redox probe, enabling quantitative cell detection using the change in current. This label-free MXene-based cytosensor platform yielded a wide linear range of 102-106 cells/mL, low detection limit of 47 cells/mL, and good sensitivity and selectivity in the detection of HER2-posetive cells in blood samples. The presented aptacytosensor demonstrates the great potential of using CoFe2O4@Ag magnetic nanohybrids and MXenes to monitor cancer progression via circulating tumor cells in blood at low cost.

Anti-bacterial and wound healing-promoting effects of zinc ferrite nanoparticles.

BACKGROUND: Increasing antibiotic resistance continues to focus on research into the discovery of novel antimicrobial agents. Due to its antimicrobial and wound healing-promoting activity, metal nanoparticles have attracted attention for dermatological applications. This study is designed to investigate the scope and bactericidal potential of zinc ferrite nanoparticles (ZnFe2O4 NPs), and the mechanism of anti-bacterial action along with cytocompatibility, hemocompatibility, and wound healing properties. RESULTS: ZnFe2O4 NPs were synthesized via a modified co-precipitation method. Structure, size, morphology, and elemental compositions of ZnFe2O4 NPs were analyzed using X-ray diffraction pattern, Fourier transform infrared spectroscopy, and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. In PrestoBlue and live/dead assays, ZnFe2O4 NPs exhibited dose-dependent cytotoxic effects on human dermal fibroblasts. In addition, the hemocompatibility assay revealed that the NPs do not significantly rupture red blood cells up to a dose of 1000 µg/mL. Bacterial live/dead imaging and zone of inhibition analysis demonstrated that ZnFe2O4 NPs showed dose-dependent bactericidal activities in various strains of Gram-negative and Gram-positive bacteria. Interestingly, NPs showed antimicrobial activity through multiple mechanisms, such as cell membrane damage, protein leakage, and reactive oxygen species generation, and were more effective against gram-positive bacteria. Furthermore, in vitro scratch assay revealed that ZnFe2O4 NPs improved cell migration and proliferation of cells, with noticeable shrinkage of the artificial wound model. CONCLUSIONS: This study indicated that ZnFe2O4 NPs have the potential to be used as a future antimicrobial and wound healing drug.

Metal oxide-based gas sensors for the detection of exhaled breath markers.

Exhaled breath test is a typical disease monitoring method for replacing blood and urine samples that may create discomfort for patients. To monitor exhaled breath markers, gas biomedical sensors have undergone rapid progress for non-invasive and point-of-care diagnostic devices. Among gas sensors, metal oxide-based biomedical gas sensors have received remarkable attention owing to their unique properties, such as high sensitivity, simple fabrication, miniaturization, portability and real-time monitoring. Herein, we reviewed the recent advances in chemoresistive metal oxide-based gas sensors with ZnO, SnO2 and In2O3 as sensing materials for monitoring a range of exhaled breath markers (i.e., NO, H2, H2S, acetone, isoprene and formaldehyde). We focused on the strategies that improve the sensitivity and selectivity of metal oxide-based gas sensors. The challenges to fabricate a functional gas sensor with high sensing performance along with suggestions are outlined.

Development of bactericidal spinel ferrite nanoparticles with effective biocompatibility for potential wound healing applications.

The current study was devised to explore the antibacterial activity and underlying mechanism of spinel ferrite nanoparticles (NPs) along with their biocompatibility and wound healing potentials. In this regard, nickel ferrite and zinc/nickel ferrite NPs were synthesized via a modified co-precipitation method and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy Energy-dispersive X-ray spectroscopy (EDX). The biocompatibility of the synthesized NPs with human dermal fibroblast (HDF) and red blood cells (RBCs) was assessed. The biocompatible concentrations of the NPs were used to investigate the antimicrobial activity against various pathogenic Gram-negative and Gram-positive bacteria. The mode of bactericidal action was also explored. In vitro scratch assay was performed to evaluate the wound healing potential of NPs. The SEM-EDX analysis showed that the average particles size of nickel ferrite and zinc/nickel ferrite were 49 and 46 nm, respectively, with appropriate elemental composition and homogenous distribution. The XRD pattern showed all the characteristic diffraction peaks of spinel ferrite NPs, which confirmed the synthesis of the pure phase cubic spinel structure. The biocompatible concentration of nickel ferrite and zinc/nickel ferrite NPs was found to be 250 and 125 µg ml-1, respectively. Both the NPs showed inhibition against all the selected strains in the concentration range of 50 to 1000 µg ml-1. Studies on the underlying antimicrobial mechanism revealed damage to the cell membrane, protein leakage, and intracellular reactive oxygen species production. The in vitro scratch assay confirmed the migration and proliferation of fibroblast with artificial wound shrinkage. This study shows that nickel ferrite and zinc/nickel ferrite NPs could be a strong candidate for antibacterial and wound healing nano-drugs.

Biodegradable ß-Cyclodextrin Conjugated Gelatin Methacryloyl Microneedle for Delivery of Water-Insoluble Drug.

Transdermal delivery of water-insoluble drugs via hydrogel-based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water-insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and ß-cyclodextrin (GelMA-ß-CD) is reported. When curcumin, an unstable and water-insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer-drug complex GelMA-ß-CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three-dimensional B16F10 melanoma models. The GelMA-ß-CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA-ß-CD MN arrays patch.

Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP-Mediated Mechanosensing.

Stem cells secrete trophic factors that induce angiogenesis. These soluble factors are promising candidates for stem cell-based therapies, especially for cardiovascular diseases. Mechanical stimuli and biophysical factors presented in the stem cell microenvironment play important roles in guiding their behaviors. However, the complex interplay and precise role of these cues in directing pro-angiogenic signaling remain unclear. Here, a platform is designed using gelatin methacryloyl hydrogels with tunable rigidity and a dynamic mechanical compression bioreactor to evaluate the influence of matrix rigidity and mechanical stimuli on the secretion of pro-angiogenic factors from human mesenchymal stem cells (hMSCs). Cells cultured in matrices mimicking mechanical elasticity of bone tissues in vivo show elevated secretion of vascular endothelial growth factor (VEGF), one of representative signaling proteins promoting angiogenesis, as well as increased vascularization of human umbilical vein endothelial cells (HUVECs) with a supplement of conditioned media from hMSCs cultured across different conditions. When hMSCs are cultured in matrices stimulated with a range of cyclic compressions, increased VEGF secretion is observed with increasing mechanical strains, which is also in line with the enhanced tubulogenesis of HUVECs. Moreover, it is demonstrated that matrix stiffness and cyclic compression modulate secretion of pro-angiogenic molecules from hMSCs through yes-associated protein activity.

Electrochemical cytosensors for detection of breast cancer cells.

Breast cancer is one of lethal cancers among women with its metastasis leading to cancer-related morbidity and mortality. Circulating tumor cells (CTCs) derived from a primary tumor can be detected in the venous blood of cancer patients. Monitoring CTCs in blood samples has increased exponentially over the past decades and holds great promise in the diagnosis and treatment of metastatic breast cancer. Electrochemical cytosensors, classified as a class of electrochemical biosensors for sensitive detection and enumeration of targeted cells with minimally invasive methods, have the advantages of electrochemical biosensors, such as simplicity, low cost, and low limit of detection. Here, we review recent progress in the detection of CTCs from breast cancer with a focus on electrochemical cytosensors. This review describes platforms benefiting from these cytosensors to identify cancerous breast cells. Furthermore, strategies for signal amplification and also generation of reusable electrochemical cytosensors are introduced. In addition, breast cancer markers and biorecognition elements for cell capturing are reviewed.