Aptamer‐integrated α‐Gal liposomes as bispecific agents to trigger immune response for killing tumor cells

Abstract

A novel bispecific α‐Gal liposome was constructed by self‐assembling AS1411 aptamers into the α‐Gal containing liposomes. The α‐Gal liposomes were prepared using cell membranes of red blood cells from rabbit, which are composed of cholesterol, phospholipids, and α‐Gal glycolipids. AS1411 is a DNA aptamer with high specificity and affinity for nucleolin and could integrate into liposomes by the modification of cholesterol. The bispecific α‐Gal liposomes surface‐functionalized by α‐Gal and AS1411 aptamer could recognize anti‐Gal antibodies and nucleolin overexpressed by tumor cells simultaneously, followed by activating the immune system to attack the tumor cells, resulting in the lysis of the tumor cells by antibody dependent cell‐mediated cytotoxicity. Under simulated tumor environment, the lysis rate of MCF‐7 cells treated by the AS1411 modified α‐Gal liposomes drastically increased compared to the liposomes without AS1411 aptamer. This study suggests that the AS1411 modified α‐Gal liposomes can recognize nucleolin‐overexpressing tumor cells selectively, subsequently improve the effect of the immunotherapy with high specificity. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1176–1183, 2019.

G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy

“…Thus, resulting in the lysis of cancer cells by antibody dependent cell-mediated cytotoxicity. After tumor environment simulation (in the presence of human blood cells, peripheral blood mononuclear cells, and human IgG), breast cancer cells (MCF-7) treated with the AS1411-liposomes presented a higher lysis rate than cells treated with liposomes without AS1411 [ 76 ]. Moreover, in the simulative tumor environment, MCF-7 cells in human blood could be targeted by AS1411-liposomes selectively and the liposomes could recruit the pre-existing anti-Gal antibodies in human blood to the surface of MCF-7 cells to induce the antibody dependent cell-mediated cytotoxicity killing of MCF-7 cells [ 76 ].…”

“…After tumor environment simulation (in the presence of human blood cells, peripheral blood mononuclear cells, and human IgG), breast cancer cells (MCF-7) treated with the AS1411-liposomes presented a higher lysis rate than cells treated with liposomes without AS1411 [76]. Moreover, in the simulative tumor environment, MCF-7 cells in human blood could be targeted The AS1411 targeted liposomes able to trigger an immune response were also developed [76]. In this case, liposomes prepared from cell membranes of red blood cells from rabbit, constituted of cholesterol, phospholipids, and α-Gal glycolipids, were functionalized (through cholesterol modification) with the AS1411 [76] The resulting liposome was able to recognize simultaneously anti-Gal antibodies and NCL overexpressed by tumor cells, followed by activating immune system to attack cancer cells.…”

“…Moreover, in the simulative tumor environment, MCF-7 cells in human blood could be targeted The AS1411 targeted liposomes able to trigger an immune response were also developed [76]. In this case, liposomes prepared from cell membranes of red blood cells from rabbit, constituted of cholesterol, phospholipids, and α-Gal glycolipids, were functionalized (through cholesterol modification) with the AS1411 [76] The resulting liposome was able to recognize simultaneously anti-Gal antibodies and NCL overexpressed by tumor cells, followed by activating immune system to attack cancer cells. Thus, resulting in the lysis of cancer cells by antibody dependent cell-mediated cytotoxicity.…”

Biosensors Made of Synthetic Functional Nucleic Acids Toward Better Human Health

“…A large proportion of aptasensors that were described in 2018 and 2019 were for general cancer biomarkers, meaning they were biomarkers that were useful for multiple cancer types. Biomarkers that were examined include PDGF-BB (LODs, 0.13 nM, 0.08 ng/mL, 0.52 nM, and 3.2 pM), − VEGF (LODs, 0.3 fM and 12 pM), − CD70 (LOD, 14 cells/mL), neutrophil gelatinase-associated lipocalin (NGAL), nucleolin, ,,, ATP (LOD, 0.01 pM), , epidermal growth factor receptor (EGFR, LODs, 5.64 fg/mL, 0.7 ng/mL, and 0.1 ng/mL), − MCF-7 cells (LOD, 61 cells/mL), telomerase (LOD, 100 cells), thymidine kinase 1 (LOD, 54 pg/mL), miRNA let-7a (LOD, 5.12 aM), cytochrome C (LOD, 25.90 nM), lysozyme (LOD, 0.94 nM), mucin 1 (LOD, 0.13 ng/mL), , epithelial cell adhesion molecule (EpCAM, LODs, 10 pM and 20 pg/mL), , N -glycolylneuraminic acid (Neu5Gc, LOD, 10 ng/mL), and CD63 exosome surface protein (LODs, 32 exosomes/μL, 73 exosomes/μL, 203 exosomes/μL). − The usefulness of many of these biosensors was evaluated in complex matrices, such as whole blood, serum, or cell lysate, or in the presence of whole cells. The strength of each of these biosensors is their diverse application to multiple cancers.…”

Methoxy polyethylene glycol–cholesterol modified soy lecithin liposomes for poorlywater‐solubleanticancer drug delivery

“…Liposomes, artificially spherical vesicles prepared from naturally derived phospholipids, are widely known as the versatile biomedical materials of choice for the successful delivery of poorly water‐soluble anticancer drugs (PWSADs) 1–5 . Comprising at least one lipid bilayer enclosed aqueous core, liposomes have several advantages for delivery of PWSADs, such as enhancing drug solubility, serving as a sustained release system, reducing the toxic effect of drugs and providing protection against drug degradation 6–8 . Among the choices available, soy lecithin (SL), a natural and unsaturated phospholipid obtained from soybean, is commonly used for liposomes preparations due to its specific advantages compared to saturated phospholipids derived from animal sources, including better stability with fewer polyunsaturated fatty acids, low risk of contaminating proteins and/or pathogens, abundant availability in both purified and nonpurified forms, and low production cost 9 .…”