A simple, rapid and sensitive sandwich immunoassay based on poly(N-isopropylacrylamide) for the detection of alpha-fetoprotein.

Alpha-fetoprotein (AFP), as a tumor marker, plays a vital role in the diagnosis of liver cancer. In this work, a novel sandwich immunoassay based on a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM), was developed for the detection of AFP. This immunoassay could realize one-step rapid reaction within 1 h, and facilitate the separation of the target molecules by incorporating PNIPAM. In this method, a conjugate of PNIPAM and capture antibody (Ab1) was successfully synthesized as a capture probe and the synthetic method of PNIPAM-Ab1 was simple, while the detection antibody (Ab2) was labeled with fluorescein isothiocyanate (FITC) to form a fluorescent detection probe. By employing a sandwich immunoassay, the method achieved quantitative determination of AFP, exhibiting a wide linear range from 5 ng/mL to 200 ng/mL and a low detection limit of 2.44 ng/mL. Furthermore, it was successfully applied to the analysis of spiked human serum samples and the screening of patients with hepatic diseases in clinical samples, indicating its potential application prospect in the diagnosis of liver cancer.

Two-Stage Targeted Bismuthene-Based Composite Nanosystem for Multimodal Imaging Guided Enhanced Hyperthermia and Inhibition of Tumor Recurrence.

A key challenge for nanomedicines in clinical application is to reduce the dose while achieving excellent efficacy, which has attracted extensive attention in dose toxicity and potential risks. It is thus necessary to reasonably design nanomedicine with high-efficiency targeting and accumulation. Here, we designed and synthesized a tetragonal bismuthene-based "all-in-one" composite nanosystem (TPP-Bi@PDA@CP) with two-stage targeting, multimodal imaging, photothermal therapy, and immune enhancement functions. Through the elaborate design of its structure, the composite nanosystem possesses multiple properties including (i) two-stage targeting function of hepatoma cells and mitochondria [the aggregation at the tumor site is 2.63-fold higher than that of traditional enhanced permeability and retention (EPR) effect]; (ii) computed tomography (CT) contrast-enhancement efficiency as high as ∼51.8 HU mL mg-1 (3.16-fold that of the clinically available iopromide); (iii) ultrahigh photothermal conversion efficiency (52.3%, 808 nm), promising photothermal therapy (PTT), and high-contrast infrared thermal (IRT)/photoacoustic (PA) imaging of tumor; (iv) benefitting from the two-stage targeting function and excellent photothermal conversion ability, the dose used in this strategy is one of the lowest doses in hyperthermia (the inhibition rate of tumor cells was 50% at a dose of 15 µg mL-1 and 75% at a dose of 25 µg mL-1); (v) the compound polysaccharide (CP) shell with hepatoma cell targeting and immune enhancement functions effectively inhibited the recurrence of tumor. Therefore, our work reduces the dose toxicity and potential risk of nanomedicines and highlights the great potential as an all-in-one theranostic nanoplatform for two-stage targeting, integrated diagnostic imaging, photothermal therapy, and inhibition of tumor recurrence.

A PdMo bimetallene with precise wavelength adjustment and catalysis for synergistic photothermal ablation and hydrogen therapy of cancer at different depths.

By delivering the idea of green and safe hydrogen energy and novel photothermal therapy to the biomedical field, engineering of therapeutic nanomaterials for treatment of major diseases (such as cancer) holds great significance. In this work, a novel PdMo bimetallene was synthesized by a solvothermal reduction method, and it was explored and applied in the field of anti-tumor therapy for the first time. The absorption peak of the PdMo bimetallene can be precisely adjusted in the NIR biological window (700-1350 nm) only by changing the synthesis time. At the same time, it also shows strong light absorption and high photothermal conversion efficiency. Specifically, the photothermal conversion efficiencies at 808 nm, 980 nm and 1064 nm are 43.1%, 51.7% and 69.15%, respectively. Surprisingly, a PdMo bimetallene is an efficient catalyst, which can effectively promote hydrogen production from the hydrolysis of ammonia borane (AB) under acidic and photothermal conditions. Benefitting from these excellent properties, a multifunctional composite nano therapeutic agent (PdMo@AB@HA) was developed via layer-by-layer surface modification with AB and hyaluronic acid (HA). In this way, the synergistic PTT/hydrogen therapy of PdMo@AB@HA composite nanosheets in the NIR-I and NIR-II windows (808 nm, 980 nm, and 1064 nm) on mouse tumor xenografts of different depths was realized. Furthermore, the controlled release of hydrogen, targeted endocytosis, efficient eradication of tumors of different depths and high biosafety were systematically proved in vitro and in vivo. This work not only provides a novel and efficient theranostic nanoplatform for efficient cancer theranostics, but also provides a new strategy for the development of safe and efficient new anti-tumor therapies.

Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer.

Cancer is a leading cause of human mortality. Given that it is difficult for conventional therapeutic approaches to effectively eradicate tumors and inhibit their recurrence and metastasis, new therapeutic strategies for solving this problem are urgently needed. In this work, we report the development of a two-dimensional titanium carbide nanocomposite drug delivery system. The system can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system. A surface modification engineering strategy has been elaborately designed to realize the multifunctionalization of an MXene, Ti3C2. In this strategy, the nanocomposite drug delivery system (Ti3C2@Met@CP) was established via layer by layer adsorption of metformin (Met) and compound polysaccharide (CP) on the surface of Ti3C2 nanosheets. Among these materials, the synthesized (AlOH)4--functionalized Ti3C2 nanosheets possess strong near-infrared absorption (extinction coefficient of 36.2 L g-1 cm-1), high photothermal conversion efficiency (∼59.6%) and effective singlet oxygen generation (1O2). Compound polysaccharide (CP) is a new immunomodulator formed by mixing lentinan, pachymaran and tremella polysaccharides in optimal proportions. Especially, the decoration of CP onto the Ti3C2 nanosheets endows Ti3C2 with a well-defined shell, improves its tumor site aggregation and biocompatibility, and activates the host's immune functions. The synergistic eradication and inhibition of tumor recurrence and metastasis have been systematically evaluated by in vivo and in vitro experiments.

A simple MWCNTs@paper biosensor for CA19-9 detection and its long-term preservation by vacuum freeze drying.

This paper introduces a cheap simple MWCNTs@paper biosensor for the detection of CA19-9, which is a biomarker of pancreatic cancer. By adding the CA19-9 antibody to the surface of MWCNTs which are deposited on the microporous filter paper, the correlation between the concentration of CA19-9 and resistance of biosensor element was linear due to the site-specific binding of antigen and antibody. The detection range is wide (0 U/mL-at least 1000 U/mL), and even in the low concentration of CA19-9, the linearity remains satisfying. Based on this property, it could be used for the detection of early-stage pancreatic cancer. Besides, this research originally introduces a vacuum freeze-drying method for the long-term preservation of biosensor, prolonging its storage time from 3 h to at least 7 days, which signifcantly promoted its value in practical application. One piece of the MWCNTs@paper biosensor only cost $2 (about 30 times cheaper than ELISA) approximately, and the detection speed is satisfying (2 h, 12 times faster than ELISA), which will possibly increase its opportunity of mass production and clinical practice.

Lentinan in-situ coated tungsten oxide nanorods as a nanotherapeutic agent for low power density photothermal cancer therapy.

Development of high photothermal performance and biocompatible nanotherapeutic agents is of great importance for photothermal cancer treatment. In this paper, we have developed lentinan decorated tungsten oxide nanorods (W18O49@LTN NRs) via a mild one-step solvothermal route. Owing to the numerous surface hydroxyl groups of polymer chains, the presence of lentinan layer in the surface of W18O49 NRs lead to good biocompatibility. The lentinan layer also affects the crystal structure of W18O49 and improves near-infrared absorption (~1.7 × 109 M-1 cm-1 at 980 nm), which is two orders of higher than previously reported PEGylated W18O49 nanowires. Even under near-infrared (NIR) laser irradiation at a very low power density of 0.4 W/cm2, the temperature of W18O49@LTN NRs aqueous dispersion (125 µg/mL) could increase by 15.1 °C. The photothermal conversion efficiency of W18O49@LTN NRs reaches 33.86%, which is higher than previously reported WO3-x hierarchical nanostructures (28.1%). Importantly, when cancer cells were treated with W18O49@LTN NRs (200 µg/mL) and 980 nm laser (0.4 W/cm2), a significant photo-induced cell killing behavior was observed. This work demonstrates that W18O49@LTN NRs have the potential for precise cancer treatment.