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Nanocarriers as an Emerging Platform for Cancer Therapy
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Dan Peer, Jeffrey M. Karp, Seungpyo Hong, Omid C. Farokhzad, Rimona Margalit, Robert Langer
It is also possible to increase binding affinity and selectivity to cell surface targets by engineering proteins that detect a specific conformation of a target receptor. In a recent in vivo study using a fusion protein consisting of an scFv antibody fragment to target and deliver small interfering RNA (siRNA) to lymphocytes—a type of white blood cell—a 10,000-fold increased affinity for the target receptor, integrin LFA-1, was observed [18]. Integrin LFA-1 is usually present in a low-affinity non-adhesive form on na¨ıve leukocytes (white blood cells that are not activated by cancer cells or pathogens that enter the body), but converts to the high-affinity adhesive form through conformational changes on activation of the immune system. Therefore, targeting the high-affinity form of LFA-1 enables drugs to be selectively delivered to the activated and adhesive leukocytes. New classes of targeting molecules can be engineered to target specific conformations. These include small protein domains, known as affibodies, that can be engineered to bind specifically to different target proteins in a conformational-sensitive manner. Other small proteins that act like antibodies—called avimers—are used to bind selectively to target receptors through multivalent effects. Nanobodies, which are heavy-chain antibodies engineered to one tenth of the size of an intact antibody with a missing light chain, have been used to bind to carcinoembryonic antigen (CEA), a protein used as a tumour marker [38–40] (Fig. 2.2b).
Controlled release of vascular endothelial growth factor (VEGF) in alginate and hyaluronic acid (ALG–HA) bead system to promote wound healing in punch-induced wound rat model
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Maqsood Ali, Si Hyun Kwak, Byong-Taek Lee, Hwan Jun Choi
For the further effect of ALG–HA/Hep in the in vivo studies, different concentrations of the VEGF were treated with the 2 × 103 CPAE cells at the time points of day 7 and day 14, as mentioned earlier for expression of the endothelial enzyme (eNOS) and vascular cells adhesion proteins (VCAM1). CPAE cells were cultured in low number to prevent over confluency. eNOS is also known under different names such as nitric oxide synthase 3 (NOS3) or constitutive NOS (eNOS). Previously, eNOS showed the induction of angiogenesis [51]. Another study mentioned wound healing in diabetic type I rats by inducing the expression levels of eNOS, VEGF and Hypoxia-inducible factor 1-alpha (HIF-1a) through a PI3K-dependent signaling pathway [52]. Firm adhesion of leucocytes is promoted by VCAM-1 and their corresponding ligands Lymphocyte function-associated antigen 1 (LFA-1) and very late antigen-4 (VLA-4). The binding of the leucocytes for transmigration promotes the wound-healing process [53, 54]. At day 7, analysis of the western blot results did not show any significant results regarding the adhesive protein marker and endothelial enzyme (Supplementary Figure S3(a–c)). Figure 7(a,b) shows the relative expressive markers of different groups at the day 14 time point. ALG–HA/VEGF150 western blot results in Figure 7(c) showed significant expression of eNOS and VCAM1. As previous studies showed low significant or non-significant protein expressions on day 7 [55]. Sustained release of the VEGF with the time might be the reason of low expression of eNOS and VCAM1 proteins in day 7 groups. As different concentrations of the VEGF were analyzed for the expression of protein in CPAE cells, ALG–HA/VEGF150 beads were suggested to be a prominent dual polymer bead system for wound healing for in vivo studies.