Dual stimulus-responsive renewable nanoadsorbent for selective adsorption of low-density lipoprotein in serum.

Selective removal of ultra-high low-density lipoprotein (LDL) from the blood of hyperlipemia patients using hemoperfusion is considered an efficient method to prevent the deterioration of atherosclerotic cardiovascular disease. Based on the exceptional structure-function properties of multistimulus-responsive materials, we developed a magnetic photorenewable nanoadsorbent (Fe3O4@SiO2@Azo-COOH) with outstanding selectivity and regenerative characteristics, featuring functionalized azobenzene as the ligand. The dual-stimulus response endowed Fe3O4@SiO2@Azo-COOH with rapid separation and photoregenerative properties. The adsorbent demonstrated excellent removal efficiency of LDL with an adsorption capacity of 15.06 mg/g, and highly repetitive adsorption performance (≥5 cycles) under irradiation. Fe3O4@SiO2@Azo-COOH also exhibited remarkable adsorption properties and selectivity in human serum, with adsorption capacities of 10.93, 21.26 and 9.80 mg/g for LDL, total cholesterol and triglycerides and only 0.77 mg/g for high-density lipoprotein (HDL), resulting in a 93% selective adsorption difference (LDL/HDL). Complete green regeneration of the nanoadsorbent was achieved through a simple regeneration process, maintaining a recovery rate of 99.4% after five regeneration experiments. By combining dynamic perfusion experiment with micromagnetic microfluidics, the LDL content decreased by 16.6%. Due to its superior adsorption capacity and regenerative properties, the dual stimulus-responsive nanosorbent is considered a potential hemoperfusion adsorbent.

TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.

Dual Stealth Functional Immuno-magnetic Nanoparticles for High-Performance Isolation of Circulating Tumor Cells.

As a biomarker of hepatocellular carcinoma (HCC) biopsy, circulating tumor cells (CTCs) are often used in the diagnosis of cancer and treatment guidance. For CTCs detection, immuno-magnetic nanoparticles (IMNs) are one of the most commonly used platforms. However, the nonspecific adsorption of proteins and non-tumor cells weakens the performance of IMNs to capture CTCs. In this work, we developed an IMNs platform which was constructed by a biomimetic protein corona precoating and a polyethylene glycol (PEG) spacer to form the PEG and corona-coated IMNs (IP-CMNs). Due to the dual stealth effect of protein corona precoating and PEG spacer, the nonspecific protein adsorption and cell binding of P-CMNs could reduce by ∼5.5- and ∼5.4-fold, respectively, compared with those of unmodified particles. Furthermore, the PEG spacer could not only reduce the interaction between IP-CMNs and leukocytes but also enhance the capture performance toward tumor cells. By using artificial blood samples, the capture efficiency of IP-CMNs toward rare CTCs was found to be 88.3%, while it was 70.5% by using commercial IMNs. Finally, CTCs were successfully isolated in all HCC patient blood samples (7/7) using IP-CMNs. These results provide insight into the use of the multifunctional nanoplatform as a useful tool for CTCs detection.

Photorenewable Azobenzene Polymer Brush-Modified Nanoadsorbent for Selective Adsorption of LDL in Serum.

The elevated concentration of low-density lipoprotein (LDL) is recognized as a leading factor of hyperlipidemia (HLP), and selective adsorption of serum LDL is regarded as a practical therapy. Based on the superior structure-function characteristics of stimuli-responsive materials, a photorenewable nanoadsorbent (SiO2@Azo@Gly) with high selectivity and reusability was developed using azobenzene as the functional ligand. Its principle was certified by the preparation of silicon nanoparticles with atom transfer radical polymerization (ATRP)-initiating groups via a sol-gel reaction and their subsequent grafting of azobenzene polymer brushes by surface-initiated ATRP, followed by modification with glycine. Immobilization of carboxylated azobenzene polymer brushes onto the nanoparticles endowed SiO2@Azo@Gly with high adsorption selectivity and reusability. The advanced nanoadsorbent exhibited excellent LDL adsorption capacity at about 27 mg/g and could be regenerated by illumination with high efficiency (circulations ≥ 5); this was further verified by transmission electron microscopy (TEM) and Fourier-transform infrared (FTIR) analysis. SiO2@Azo@Gly also demonstrated superior adsorption efficiency and selectivity in serum from HLP patients, the respective adsorption capacities of LDL, triglyceride, and total cholesterol were about 15.65, 24.48, and 28.36 mg/g, and the adsorption to high-density lipoprotein (cardioprotective effect) was only about 3.66 mg/g. Green regeneration of the nanoadsorbent could be achieved completely through a simple photoregeneration process, and the recovery rate was still 97.9% after five regeneration experiments.

Amphiphilic shell nanomagnetic adsorbents for selective and highly efficient capture of low-density lipoprotein from hyperlipidaemia serum.

Removal of low-density lipoprotein (LDL) from hyperlipemia patients' blood represents an effective approach to prevent the progression of atherosclerotic cardiovascular disease. Based on the LDL structural characteristics and intermolecular interactions, a tailored nano-adsorbent (Fe3O4@SiO2@PAA-PE) was prepared aimed at the removal of LDL from hyperlipemia serum with high selectivity. The core-shell structured magnetic nanoparticles were embedded in an amphiphilic layer composed of hydrophilic poly(acrylic acid) and lipophilic phospholipids to provide multifunctional binding for LDL particles. The results of dynamic light scattering, water contact angle and zeta-potential measurements, thermal gravimetric analysis, and X-ray photoelectron spectroscopy together with Fourier transform infrared spectroscopy confirmed the core-shell structured nanoparticles bearing amphiphilic poly acrylic acid and phospholipid molecules. Because of the superior electronegativity of the functional layer, the nano-adsorbent demonstrated favorable adsorption selectivity against high-density lipoprotein, which possesses a similar structure to LDL but has a cardio-protective function in the human body. The respective adsorption capacity of Fe3O4@SiO2@PAA-PE towards LDL, total cholesterol and triglycerides reached up to 6.26 mg g-1, 8.41 mg g-1 and 9.19 mg g-1, which was 7.03, 9.45 and 10.32 times that towards HDL (0.89 mg g-1). The kinetic and isothermal studies revealed that multiple interactions containing both physical and chemical adsorption occurred in the binding procedure between LDL and Fe3O4@SiO2@PAA-PE, and chemical adsorption may play a more predominant role in LDL adsorption. The nano-adsorbent also had negligible effects on blood cells, and possessed satisfactory recyclability, low cytotoxicity and hemolysis ratios, indicating its good application prospects as a hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Protein corona-coated immunomagnetic nanoparticles with enhanced isolation of circulating tumor cells.

Immunomagnetic nanoparticles (IMNs) have been widely developed as a detection tool to isolate rare circulating tumor cells (CTCs) from whole blood as a potential method for early cancer diagnosis, metastasis examination, and treatment guidance. However, a spontaneous interaction between nanoparticles and proteins results in the formation of a protein corona that reduces the performance of IMNs when they enter body fluids. To address this issue, the protein corona was precoated onto magnetic nanoparticles (C-MNs), and then their surfaces were conjugated with an immuno-antibody. The adsorption of proteins on C-MNs was decreased 6-fold and non-specific cell binding was reduced 5-fold, compared with magnetic nanoparticles (MNs). Furthermore, the immuno-antibody functionalized C-MNs (IC-MNs) maintained highly specific CTC capture performance when exposed to blood plasma. By using artificial spiked blood samples, IC-MNs exhibited 90.2% CTC isolation efficiency, compared with 60.3% by using IMNs. IC-MNs also successfully captured CTCs with high purity in 24 out of 26 female breast cancer patient blood samples. This work demonstrated that a novel preformed protein corona strategy can provide a useful clinically applicable diagnostic tool.

Biomembrane-mimetic hemoperfusion adsorbent for efficient removal of low-density lipoprotein from hyperlipemia blood.

Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Hydroxyapatite reinforced inorganic-organic hybrid nanocomposite as high-performance adsorbents for bilirubin removal in vitro and in pig models.

Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity, poor mechanical strength and low biocompatibility of adsorbents. In this work, a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane (VTES)-functionalized hydroxyapatite nanoparticles (V-Hap) and non-ionic styrene-divinylbenzene (PS-DVB) resins (PS-DVB/V-Hap) using suspension polymerization. Notably, our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer, with the hardness and modulus increasing by nearly 3 and 2.5 times, respectively. Moreover, due to the development of a mesoporous structure, the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg g-1. More importantly, the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility. Furthermore, in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models, and this material could potentially prevent liver damage and improve clinical outcomes. Taken together, the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion, thus replacing the existing techniques where plasma separation is initially required.

Targeting regulation of the tumour microenvironment induces apoptosis of breast cancer cells by an affinity hemoperfusion adsorbent.

The cytokine network of tumour microenvironment (TME) plays an important role in cancer growth and progression. The current work aims to provide a new strategy for cancer therapy based on the targeted regulation of cytokines in the TME. Here, heparin-coupled polyvinyl alcohol (PVA-H) microspheres have been developed as an adsorbent for selectively remove tumour-induced immunosuppressive cytokines, such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß), but not tumour necrosis factor-alpha (TNF-α) which has an immune-stimulating effect and can inhibit tumour growth. The proliferation and apoptosis of breast cancer cells after perfusion were tested by cell viability assays, flow cytometry analysis and mRNA microarray assays. Results showed that the PVA-H microspheres efficiently absorbed the majority of VEGF (74.39%) and TGF-ß (86.39%), but much less TNF-α (4.16%). The regulation of the cytokines had remarkable anti-proliferative and pro-apoptotic effects on breast cancer cells, which was further confirmed from the change of mRNA expression levels. Thus, targeting regulatory pathways within the TME by an affinity adsorbent that selectively depletes immunosuppressive cytokines is potentially a new and promising strategy for cancer therapy.