E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating tumor cells

Abstract

The presence of circulating tumor cells (CTCs) is believed to lead to the formation of secondary tumors via an adhesion cascade involving interaction between adhesion receptors of endothelial cells and ligands on CTCs. Many CTCs express sialylated carbohydrate ligands on their surfaces that adhere to selectin protein found on inflamed endothelial cells. We have investigated the feasibility of using immobilized selectin proteins as a targeting mechanism for CTCs under flow. Herein, targeted liposomal doxorubicin (L-DXR) was functionalized with recombinant human E-selectin (ES) and polyethylene glycol (PEG) to target and kill cancer cells under shear flow, both when immobilized along a microtube device or sheared in a cone-and-plate viscometer in a dilute suspension. Healthy circulating cells such as red blood cells were not targeted by this mechanism and were left to freely circulate, and minimal leukocyte death was observed. Halloysite nanotube (HNT)-coated microtube devices immobilized with nanoscale liposomes significantly enhanced the targeting, capture, and killing of cancer cells. This work demonstrates that E-selectin functionalized L-DXR, sheared in suspension or immobilized onto microtube devices, provides a novel approach to selectively target and deliver chemotherapeutics to CTCs in the bloodstream.

Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

“…Numerous targeted nanoparticles against different antigens have been described in the literature for potential treatment of solid tumors (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The majority of those studies focused on the selection and design of nanoparticles and/or targeting moieties.…”

Properties and applications of halloysite nanotubes: recent research advances and future prospects

“…Based on its molar mass also called molar weight (MW), guests loaded on Hal could be listed in either of the following categories: i) low MW substances with MW b 300 g/mol, e.g., propranolol hydrochloride (Levis and Deasy, 2003), 5-aminosalicylic (Viseras et al, 2008(Viseras et al, , 2009Aguzzi et al, 2013), benzotriazole (Shchukin and Mohwald, 2007;Abdullayev et al, 2009;Abdullayev and Lvov, 2010), 8-hydroxyquinoline (Fix et al, 2009), glycerol (Suh et al, 2011), stearic acid (Mei et al, 2011a), capric acid (Mei et al, 2011b), resveratrol (Vergaro et al, 2012), ibuprofen (Tan et al, , 2014b, and 5-fluorouracil (Rao et al, 2014); ii) medium MW substances with 300 g/mol b MW b 1000 g/mol, e.g., dexamethasone, furosemide, nifedipine (Veerabadran et al, 2007(Veerabadran et al, , 2009, fentanyl (Forsgren et al, 2010), doxorubicin (Mitchell et al, 2012), and orange II (Yuan et al, 2012b); iii) high MW substances with MW N 1000 g/mol, e.g., metalloporphyrins (Machado et al, 2008), α-amylase , urease (Shchukin et al, 2005;Zhai et al, 2010), antisense oligonucleotides (Shi et al, 2011), and insulin .…”

Escalating Applications of Halloysite Nanotubes

“…HNTscoated microtube devices immobilized with nanoscale liposomes appreciably improved the targeting, capturing and killing of cancer cells. This work provides a novel approach to selectively target and deliver chemotherapeutics to CTCs in the bloodstream 84 . Microtube surfaces with immobilized HNTs and E-selectin functionalized liposomal doxorubicin (ESPEG L-DXR) considerably enlarged the number of breast adenocarcinoma MCF7 cells captured during flow; however also notably decrease the number of captured neutrophils.…”