Kiwi-Inspired Rational Nanoarchitecture with Intensified and Discrete Magneto-Fluorescent Functionalities for Ultrasensitive Point-of-Care Immunoassay.

Fluorescent lateral flow immunoassays (FLFIA) is a well-established rapid detection technique for quantitative analysis. However, achieving accurate analysis of biomarkers at the pg mL-1 level using FLFIA still poses challenges. Herein, an ultrasensitive FLFIA platform is reported utilizing a kiwi-type magneto-fluorescent silica nanohybrid (designated as MFS) that serves as both a target-enrichment substrate and an optical signal enhancement label. The spatially-layered architecture comprises a Fe3O4 core, an endocarp-fibers like dendritic mesoporous silica, seed-like quantum dots, and a kiwi-flesh like silica matrix. The MFS demonstrates heightened fluorescence brightness, swift magnetic response, excellent size uniformity, and dispersibility in water. Through liquid-phase capturing and fluorescence-enhanced signal amplification, as well as magnetic-enrichment sample amplification and magnetic-separation noise reduction, the MFS-based FLFIA is successfully applied to the detection of cardiac troponin I that achieved a limit of detection at 8.4 pg mL-1, tens of times lower than those of previously published fluorescent and colorimetric lateral flow immunoassays. This work offers insights into the strategic design of magneto-fluorescent synergetic signal amplification on LFIA platform and underscores their prospects in high-sensitive rapid and on-site diagnosis of biomarkers.

Compact Magneto-Fluorescent Colloids by Hierarchical Assembly of Dual-Components in Radial Channels for Sensitive Point-of-Care Immunoassay.

Exploring signal amplification strategies to enhance the sensitivity of lateral flow immunoassay (LFIA) is of great significance for point-of-care (POC) testing of low-concentrated targets in the field of in vitro diagnostics. Here, a highly-sensitive LFIA platform using compact and hierarchical magneto-fluorescent assemblies as both target-enrichment substrates and optical sensing labels is demonstrated. The large-pored dendritic templates are utilized for high-density incorporation of both superparamagnetic iron oxide nanoparticles (IOs) and quantum dots (QDs) within the vertical channels. The hierarchical structure is built via affinity-driven assembly of IOs and QDs from organic phase with silica surface and mercapto-organosilica intermediate layer, respectively. The sequential assembly with central-radial channels enables 3D loading of dual components and separately controlling of discrete functionalities. After the alkyl-organosilica encapsulation and silica sealing, the composite spheres exhibit high stabilities and compatibility with LFIA for procalcitonin (PCT) detection. With the assistance of liquid-phase antigen-capturing, magnetic enrichment, and fluorescence-signal amplification, a limit of detection of 0.031 ng mL-1 for PCT is achieved with a linear range from 0.012 to 10 ng mL-1 . The current LFIA is robust and validated for PCT detection in real serum, which holds great diagnostic significance for precise guidance of antibiotic therapy with POC manner.

Single-Nanoparticle Cell Barcoding by Tunable FRET from Lanthanides to Quantum Dots.

Fluorescence barcoding based on nanoparticles provides many advantages for multiparameter imaging. However, creating different concentration-independent codes without mixing various nanoparticles and by using single-wavelength excitation and emission for multiplexed cellular imaging is extremely challenging. Herein, we report the development of quantum dots (QDs) with two different SiO2 shell thicknesses (6 and 12 nm) that are coated with two different lanthanide complexes (Tb and Eu). FRET from the Tb or Eu donors to the QD acceptors resulted in four distinct photoluminescence (PL) decays, which were encoded by simple time-gated (TG) PL intensity detection in three individual temporal detection windows. The well-defined single-nanoparticle codes were used for live cell imaging and a one-measurement distinction of four different cells in a single field of view. This single-color barcoding strategy opens new opportunities for multiplexed labeling and tracking of cells.

Platelet Rich Plasma Loaded Multifunctional Hydrogel Accelerates Diabetic Wound Healing via Regulating the Continuously Abnormal Microenvironments.

Continuous oxidative stress and cellular dysfunction caused by hyperglycemia are distinguishing features of diabetic wounds. It has been a great challenge to develop a smart dressing that can accelerate diabetic wound healing through regulating abnormal microenvironments. In this study, a platelet rich plasma (PRP) loaded multifunctional hydrogel with reactive oxygen species (ROS) and glucose dual-responsive property is reported. It can be conveniently prepared with PRP, dopamine (DA) grafted alginate (Alg-DA), and 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol (ABO) conjugated hyaluronic acid (HA-ABO) through ionic crosslinks, hydrogen-bond interactions, and boronate ester bonds. The hydrogel possesses injectability, moldability, tissue adhesion, self-healing, low hemolysis, and hemostasis performances. Its excellent antioxidant property can create a low oxidative stress microenvironment for other biological events. Under an oxidative stress and/or hyperglycemia state, the hydrogel can degrade at an accelerated rate to release a variety of cytokines derived from activated blood platelets. The result is a series of positive changes that are favorable for diabetic wound healing, including fast anti-inflammation, activated macrophage polarization toward M2 phenotype, promoted migration and proliferation of fibroblasts, as well as expedited angiogenesis. This work provides an efficient strategy for chronic diabetic wound management and offers an alternative for developing a new-type PRP-based bioactive wound dressing.

Quantum dots assembly enhanced and dual-antigen sandwich structured lateral flow immunoassay of SARS-CoV-2 antibody with simultaneously high sensitivity and specificity.

Exploring reliable and highly-sensitive SARS-CoV-2 antibody diagnosis by point-of-care (POC) manner, holds great public health significance for extensive COVID-19 screening and controlling. Unfortunately, the currently applied gold based lateral flow immunoassay (GLFIA) may expose both false-negative and false-positive interpretations owing to the sensitivity and specificity limitations, which may cause significant risk and waste of public resources for large population screening. To simultaneously overcome the drawbacks of GLFIA, a novel fluorescent LFIA based on signal amplification and dual-antigen sandwich structure was established with largely improved sensitivity and specificity. The compact three-dimensional incorporation of hydrophobic quantum dots within dendritic affinity templates and multilayer surface derivation guaranteed a high and robust fluorescence of single label, which lowered the false negative rate of GLFIA prominently. A dual-antigen sandwich structure using labeled/immobilized SARS-CoV-2 spike receptor binding domain antigen for capturing total human SARS-CoV-2 antibody was developed, instead of general indirect antibody capturing approach, to reduce the false positive rate of GLFIA. Over 300 cases of COVID-19 negative and 97 cases of COVID-19 positive samples, the current assay revealed a 100% sensitivity and 100% specificity confirmed by both polymerase chain reaction (PCR) and chemiluminescence immunoassay (CLIA), compared with the considerable misinterpretation cases by currently applied GLFIA. The quantitative results verified by receiver operating characteristic curve and other statistical analysis indicated a well-distinguished positive/negative sample groups. The proposed strategy is highly sensitive towards low concentrated SARS-CoV-2 antibody serums and highly specific towards serums from COVID-19 negative persons and patients infected by other viruses.

Central-radial bi-porous nanocatalysts with accessible high unit loading and robust magnetic recyclability for 4-nitrophenol reduction.

Central-radial bi-porous nanocatalysts were synthesized by derivation from dendritic porous supports with hierarchical inorganic functional layers. The nanostructure exhibited a high unit loading capacity, accessible internal catalytic sites and protective mesoporous shell encapsulation. The nanocatalysts were utilized for efficient and stable heterogeneous catalytic reduction of 4-nitrophenol to 4-aminophenol with robust magnetic recyclability.

Hierarchical Plasmonic-Fluorescent Labels for Highly Sensitive Lateral Flow Immunoassay with Flexible Dual-Modal Switching.

Lateral flow immunoassay (LFIA), as a prominent point-of-care (POC) test platform, has been extensively adopted for rapid, on-site, and facile diagnosis of pathogen infections and disease biomarkers. Exploring novel structured optical labels of LFIA with amplified signal and complementary detection modes favors the sensitive and flexible POC diagnosis. Here, bimodal labels with both colorimetric and fluorescent readout were fabricated via a layered sequential assembly strategy based on affinity templates and hydrophobic metal-containing nanounits. High-quality colorimetric and fluorescent nanoparticles were densely incorporated into the colloidal supports and confined in separated regions, without interfering with each other. The hierarchical integration of gold nanoparticles and quantum dots with high loading density and good optical preservation realized dual readout and amplified signals from the assemblies of individual single nanoparticles. The "all-in-one" optical labels allowed both colorimetric and fluorescent detection of cystatin C (Cys C) after surface conjugation with antibodies. The LFIA strips revealed noninterfering dual signals for both visual inspection and quantitative detection of Cys C via the naked eye and portable devices, respectively. The limits of detection by colorimetric and fluorescent modes were 0.61 and 0.24 ng mL-1, respectively. The novel LFIA platform demonstrated sensitive, specific, and reproducible POC testing of biomarkers with flexible detection modes and was reliable for clinical diagnosis.

Polydopamine-Derivated Hierarchical Nanoplatforms for Efficient Dual-Modal Imaging-Guided Combination in Vivo Cancer Therapy.

Exploring multifunctional nanomaterials from biocompatible constituents, with integrated imaging and targeted combination therapeutic modalities of tumors in vivo, provides great prospects for clinical cancer theranostic applications. Here, we report a combination strategy for functionalization of polydopamine (PDA) nanohosts with magnetic response and stimuli-controlled drug release capabilities for in vivo cancer theranostic. The high processability of PDA as nanotemplates and surface coating layers as well as its natural affinity to metals facilitated the sandwich of a compact iron oxide nanoparticle layer into the PDA matrix, realizing enhanced near-infrared (NIR) photothermal conversion and strong superparamagnetic responsiveness. Additionally, the high reactivity of the PDA surface allowed facile linkage with reduction-responsive prodrugs and polyethylene glycol chains for in vivo chemotherapy of cancer. Under the magnetic resonance imaging/photoacoustic imaging dual-modal tumor imaging and active magnetic tumor targeting of the nanoagents in vivo, the effective tumor eradication was achieved via synergetic NIR photothermal ablation and anticancer drug delivery.

Improved Total Synthesis and Biological Evaluation of Coibamide A Analogues.

To enable the large-scale synthesis of coibamide A, we developed an improved synthetic strategy for this class of cyclodepsipeptide. The versatility of the synthetic procedure was demonstrated by the preparation of a series of designed coibamide A analogues, which enabled the preliminary structure-activity relationship (SAR) studies for this compound. Although most modifications of coibamide A resulted in decrease or loss of the antiproliferativity, we found that versatile substitution at position 3 was well tolerated. Remarkably, a simplified analogue, [MeAla3-MeAla6]-coibamide (1f), not only showed nearly the same inhibition as coibamide A against the tested cancer cells but also significantly inhibited tumor growth in vivo. The improved synthetic strategy and the relevant trends of SAR disclosed in this study will be valuable for further optimization of the overall profile of coibamide A.

Targeting Polo-like Kinase 1 by a Novel Pyrrole-Imidazole Polyamide-Hoechst Conjugate Suppresses Tumor Growth In Vivo.

The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide-Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle-regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988-1002. ©2018 AACR.

Iron oxide nanoparticle layer templated by polydopamine spheres: a novel scaffold toward hollow-mesoporous magnetic nanoreactors.

Superparamagnetic iron oxide nanoparticle layers with high packing density and controlled thickness were in situ deposited on metal-affinity organic templates (polydopamine spheres), via one-pot thermal decomposition. The as synthesized hybrid structure served as a facile nano-scaffold toward hollow-mesoporous magnetic carriers, through surfactant-assisted silica encapsulation and its subsequent calcination. Confined but accessible gold nanoparticles were successfully incorporated into these carriers to form a recyclable catalyst, showing quick magnetic response and a large surface area (642.5 m(2) g(-1)). Current nano-reactors exhibit excellent catalytic performance and high stability in reduction of 4-nitrophenol, together with convenient magnetic separability and good reusability. The integration of compact iron oxide nanoparticle layers with programmable polydopamine templates paves the way to fabricate magnetic-response hollow structures, with high permeability and multi-functionality.

Multifunctional magnetic silica nanotubes for MR imaging and targeted drug delivery.

A multifunctional drug delivery vehicle consisting of a tubular shaped silica host, a compact superparamagnetic iron oxide nanoparticle layer and a hyaluronic acid surface coating was developed as a theranostic platform, for in vivo MR imaging and magnetically guided/cancer targeted drug delivery.

A folate-integrated magnetic polymer micelle for MRI and dual targeted drug delivery.

This paper devotes a novel micellar structure for cancer theranostics by incorporating magnetic and therapeutic functionalities into a natural sourced targeting polymer vehicle. Heparin-folic acid micelles taking advantage of both excellent loading capability and cancer targeting ability have been employed to simultaneously incorporate superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin through an ultrasonication-assisted microemulsion method. In this system, folic acids not only take the responsibility of micelle construction, but also facilitate cellular uptake due to their specific reorganization by MCF-7 cells over-expressing folate receptors. The obtained micelles exhibit good colloidal stability, a high magnetic content, considerable drug loading and sustained in vitro drug release. These clustered SPIONs exhibited high r2 relaxivity (243.65 mM(-1) s(-1)) and further served as efficient probes for MR imaging. Notably, the transport efficiency of these micelles could be significantly improved under an external magnetic field, owing to their quick magnetic response. As a result, the as-proposed micelle shows great potential in multimodal theranostics, including active targeting, MRI diagnosis and drug delivery.