Bio-inspired dual-functional phospholipid-poly(acrylic acid) brushes grafted porous poly(vinyl alcohol) beads for selective adsorption of low-density lipoprotein.

Elevated levels of low-density lipoproteins (LDL) are recognized as a crucial indicator of hyperlipidemia (HLP) and lowering of LDL levels represents an effective clinical treatment strategy. Inspired by the conjugation of phospholipid monolayers and the lipid content of the LDL particle, the current study describes the preparation of an innovative hemoperfusion adsorbent. The adsorbent was prepared by attachment of phosphatidyl ethanolamine to poly(acrylic acid) modified poly(vinyl alcohol-co-triallyl isocyanurate) beads (PVA@PAA-PE). The interaction between LDL and adsorbent mimics the lipoprotein microemulsion present in the blood and thus promotes efficient binding with high affinity. In vitro adsorption using serum from patients with HLP revealed that the LDL adsorption of PVA@PAA-PE was 4.44 times higher than that of controls and the removal rate of LDL using PVA@PAA-PE was about twice as high as that of the anti-atherogenic high-density lipoprotein (HDL). In vivo whole blood perfusion demonstrated the superior affinity of PVA@PAA-PE for LDL since LDL concentration was significantly reduced from 10.71 ± 2.36 mmol L-1 to 6.21 ± 1.45 mmol L-1, while the HDL level was not severely reduced (from 0.98 ± 0.12 mmol L-1 to 0.56 ± 0.15 mmol L-1). Additionally, PVA@PAA-PE exhibited excellent hemocompatibility and low cytotoxicity. Therefore, PVA@PAA-PE is a potential adsorbent for whole blood perfusion to treat hyperlipidemia.

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.