Early detection and timely intervention play a vital role in the effective management of Alzheimer’s disease. Currently, the diagnostic accuracy for Alzheimer’s disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve diagnostic accuracy. Herein, we report a printed electrochemical biosensor based on vertical graphene (VG) modified with gold nanoparticles (VG@nanoAu) for the simultaneous detection of four Alzheimer’s disease blood biomarkers. The printed electrochemical electrode array was constructed by laser etching and inkjet printing. Then gold nanoparticles were modified onto the working electrode surface via electrodeposition to further improve the sensitivity of the sensor. In addition, the entire printed electrochemical sensing system incorporates an electrochemical micro-workstation and a smartphone. The customized electrochemical micro-workstation incorporates four electro-chemical control chips, enabling the sensor to simultaneously analyze four biomarkers. Consequently, the printed electrochemical sensing system exhibits excellent analytical performance due to the large surface area, biocompatibility, and good conductivity of VG@nanoAu. The detection limit of the sensing system for Aβ40, Aβ42, T-tau, and P-tau181 was 0.072, 0.089, 0.071, and 0.051 pg/mL, respectively, which meets the detection requirements of Alzheimer’s disease blood biomarkers. The printed electrochemical sensing system also exhibits good specificity and stability. This work has great value and promising prospects for early Alzheimer’s disease diagnosis using blood biomarkers.
Magnetic resonance imaging (MRI) guidance in the realm of anticancer therapy is crucial to visualize the spread of tumors in deep tissues, accumulate the therapeutics, and trigger them for precise therapy. Recent studies bridge this gap by integrating MRI contrast agents (CAs) with different therapeutic regimes for a better outcome. In this context, manganese-based materials hold great potential owing to their T1/T2 dual-modal MR-relaxation, less toxicity, and other therapeutic capabilities such as chemodynamic therapy, immunotherapy, etc., which have gained increasing interest among researchers and medical professionals. This work offers a timely update on the last three years for Mn-based MRI-guided theranostic applications, including chemodynamic therapy, chemotherapy, photo therapies, sonodynamic therapy, and radiotherapy against cancer. Further, several combinatory therapies and surgical intersections have also been summarized in the light of MRI guidance. The design rationale of these Mn-based agents has been discussed to understand the existing challenges and plausible outcomes shortly. Herein, we deep dive into the stimulus-based probes including pH, temperature, etc. to show the unexplored potential of Mn-complexes in this domain. This state-of-the-art review will guide innovations in Mn-based CAs to expedite safer anticancer theranostic modules for clinical translation.
18 October 2022 in Frontiers in Bioengineering and Biotechnology
Alzheimer’s disease (AD) is a neurodegenerative disease caused by neurons damage in the brain, and it poses a serious threat to human life and health. No efficient treatment is available, but early diagnosis, discovery, and intervention are still crucial, effective strategies. In this study, an electrochemical sensing platform based on a superwettable microdroplet array was developed to detect multiple AD biomarkers containing Aβ40, Aβ42, T-tau, and P-tau181 of blood. The platform integrated a superwettable substrate based on nanoAu-modified vertical graphene (VG@Au) into a working electrode, which was mainly used for droplet sample anchoring and electrochemical signal generation. In addition, an electrochemical micro-workstation was used for signals conditioning. This superwettable electrochemical sensing platform showed high sensitivity and a low detection limit due to its excellent characteristics such as large specific surface, remarkable electrical conductivity, and good biocompatibility. The detection limit for Aβ40, Aβ42, T-tau, and P-tau181 were 0.064, 0.012, 0.039, and 0.041 pg/ml, respectively. This study provides a promising method for the early diagnosis of AD.
Lupus nephritis (LN) is a common and refractory inflammation of the kidneys caused by systemic lupus erythematosus. Diagnosis and therapies at this stage are inefficient or have severe side effects. In recent years, nanomedicines show great potential for imaging diagnosis and controlled drug release. Herein, we developed a polydopamine (PDA)-based nanocarrier modified with Fe3O4 and Pt nanoparticles and loaded with necrostatin-1 (Nec-1) for the bimodal imaging and therapy of LN. Results demonstrate that Nec-1/PDA@Pt-Fe3O4 nanocarrier exhibits good biocompatibility. Nec-1, as an inhibitor of receptor-interacting protein 1 kinase, can be used to inhibit receptor-interacting protein 1 kinase activity and then reduces inflammation due to LN. Experiments in vitro and in the LN mouse model confirmed that the nanocarrier can reduce neutrophil extracellular traps (NETs) production by RIPK1 and alleviate the progression of inflammation. Previous studies proved that Pt nanoparticles can catalyze H2O2 to produce oxygen. A blood oxygen graph of mouse photoacoustic tomography confirmed that Nec-1/PDA@Pt-Fe3O4 can generate oxygen to fight against the hypoxic microenvironment of LN. PDA and Fe3O4 are used as photographic developers for photoacoustic or magnetic resonance imaging. The preliminary imaging results support Nec-1/PDA@Pt-Fe3O4 potential for photoacoustic/magnetic resonance dual-mode imaging, which can accurately and non-invasively monitor microscopic changes due to diseases. Nec-1/PDA@Pt-Fe3O4 combining these advantages exhibited outstanding performance in LN imaging and therapy. This work offers valuable insights into LN diagnosis and therapy.
Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers.Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA.Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees.Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.