The cerasomes that contain maleimide terminal groups were incubated with the thiolated anti-EGFR mAbs at a 1,385:1 lipid/antibody molar ratio for 24 hr to prepare immunocerasomes. of immunocerasomes to MG-101 A431 cells. strong class=”kwd-title” Keywords: Organic-inorganic hybrid lipid nanovesicles, Anti-EGFR antibody, Selective targeting, Cancer cells MG-101 1.?Introduction Selective targeting is an important parameter in the design and synthesis of therapeutic and/or imaging nanocarriers. Conventionally, the enhanced permeability and retention (EPR) effect in tumor vasculature has been exploited for the selective targeting of macromolecular drugs or drug-loaded nanocarriers to cancer cells [1]. A long circulation time is necessary for drugs or drug-loaded carriers to accumulate in tumor tissues, much more than in normal tissues. This, however, does not completely prevent drugs or drug-loaded carriers from accumulating in healthy tissues and causing tissue damage [2,3]. Compared to the passive EPR-targeting selective delivery, ligands that are specific to cell-surface receptors can be conjugated to nanoparticles, creating therapeutic and/or imaging nanocarriers with an improved ability to selectively target cancer cells [4,5]. Various ligands, including short peptides [4], aptamers [6] and antibodies [5], have been exploited for selective targeting. Of note, antibodies that specifically bind to cell-surface receptors enable the selective delivery of drug-loaded carries to target cells and may possess therapeutic effects as well [7]. As an example, anti-CD20 antibodies selectively bind to and kill CD20-expressing B-lymphoma cells [8]. In this study, epidermal growth MG-101 factor receptors (EGFR), which are overexpressed by several human cancers [9], are exploited as a promising target for the selective delivery of nanocarriers. Specifically, organic-inorganic liposomal cerasomes are conjugated with anti-EGFR monoclonal antibodies (mAbs) that target the EGFR glycoproteins on cell surfaces [10], creating immunocerasomes for selective delivery. Previously, Leung et al. reported the engineering of cerasomes with greatly enhanced morphological stability over conventional liposomes [11]. As membrane-mimetic nanocarriers, liposomes are among the first drug carriers that have been used in clinical applications [12]. Notably, membrane-mimetic materials display an impressive ability to inhibit platelet adhesion/activation, suppress protein adsorption, and retain the bioactivities of immobilized biomolecules [13,14]. Consequently, biomedical devices such as stents and nanoparticle-based carriers can be coated with phospholipid polymers, acquiring excellent blood compatibility and creating membrane-mimetic structures that can be readily functionalized with different bioactive molecules [14,15]. However, membrane-mimetic materials often lack sufficient morphological stability. A variety of strategies have been proposed to improve their biochemical and physical stabilities, so that their applications may be extended to areas in which durability is highly relevant [16]. An organic-inorganic hybridization approach has thus been utilized to engineer highly stable liposomal cerasomes in which the phosphate heads of phospholipids are replaced with triethoxysilyl moieties [17,18]. The hydrolysis and polymerization of triethoxysilyl moieties and the subsequent formation of polysiloxane networks on the Rabbit Polyclonal to KLRC1 surfaces of cerasomes render the lipid nanovesicles morphologically stable. The use of cerasomes as nanocarriers in gene [17] and drug delivery [11,19] has been examined. Herein, the ability of anti-EGFR-conjugated immunocerasomes to selectively target cancer cells is investigated. In the present study, organic-inorganic liposomal cerasomes are prepared using a combined sol-gel and self-assembly process and anti-EGFR mAbs are conjugated to cerasomes via maleimide-thiol coupling chemistry, creating immunocerasomes. Fluorescent lipid NBD-DPPE is also included in the preparation of immunocerasomes, enabling the imaging analysis of cellular uptake, internalization, and intracellular trafficking of the lipid MG-101 nanovesicles. Next, EGFR expression is examined in A431 epidermoid carcinoma cells, DU145 prostate carcinoma cells, and HL-60 MG-101 acute promyelocytic leukemia cells, and the selective targeting of immunocerasomes to the three cell lines is analyzed. This is to establish a correlation between the selective delivery of immunecerasomes and the differing EGFR expression by the target cells. Last, the inhibitory effects of immunocerasomes on cell proliferation are investigated. It has been.