ICAM-1 targeting of doxorubicin-loaded PLGA nanoparticles to lung epithelial cells

Abstract

Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphoctytes and intercellular adhesion molecule-1 (ICAM-1) on epithelial cells controls leukocyte adhesion, spreading, and extravasation. This process plays an important role in leukocyte recruitment to a specific site of inflammation and has been indentified as a biomarker for certain types of carcinomas. Cyclo-(1,12)-PenITDGEATDSGC (cLABL) has been shown to inhibit LFA-1 and ICAM-1 interaction via binding to ICAM-1. In addition, cLABL has been shown to internalize after binding ICAM-1. The possibility of using cLABL conjugated nanoparticles (cLABL-NP) as a targeted and controlled release drug delivery system has been investigated in this study. The cLABL peptide was conjugated to a modified Pluronic® surfactant on poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles. The cLABL-NP showed more rapid cellular uptake by A549 lung epithelial cells compared to nanoparticles without peptide. The specificity of ICAM-1 mediated internalization was confirmed by blocking the uptake of cLABL-NP to ICAM-1 using free cLABL peptide to block the binding of cLABL-NP to ICAM-1 on the cell surface. Cell studies suggested that cLABL-NPs targeted encapsulated doxorubicin to ICAM-1 expressing cells. Cytotoxicity assay confirmed the activity of the drug incorporated in nanoparticles. Sustained release of doxorubicin afforded by PLGA nanoparticles may enable cLABL-NP as a targeted, controlled release drug delivery system.

Docetaxel immunonanocarriers as targeted delivery systems for HER2-positive tumor cells: preparation, characterization, and cytotoxicity studies

“…Higher uptake of targeted nanoparticles by SKBR3 cells was in agreement with a previous study. 26 These results also suggest that immunonanoparticles may be taken up more rapidly than nontargeted nanoparticles.…”

Multifunctional Nanoparticles for Theranostic Applications

“…In this study, the cytotoxicity of four different treatments (IDNP w/o laser treatment, AIDNP w/o laser treatment, IDNP w/ laser treatment and AIDNP w/ laser treatment) were investigated. Cells were seeded into a 96-well plate on the first day, and after overnight incubation they were exposed to different treatments The slow sustained release of DOX from targeted AIDNP and the biphasic behavior of the release profile observed in both AIDNP and IDNP are consistent with other literature reports as well (Yang 2007;Chittasupho 2009;. The two phases of DOX release correspond to an initial burst release, followed by a sustained slow release.…”

Biodistribution and endocytosis of ICAM-1-targeting antibodies versus nanocarriers in the gastrointestinal tract in mice

“…ICAM-1 was selected based on: (a) its presence on GI epithelial cells 35,36 and overexpression under GI pathology; [36][37][38][39] (b) its ability to mediate binding and endocytosis of drug conjugates and carriers; 46 and (c) prior literature on ICAM-1-targeting in cell culture and in vivo. [41][42][43][44]47 We utilized model polystyrene NCs since: (a) polymer-based carriers are stable in the GI environment compared to other formulations; 7,33 Cross-sectional dissections were made in the stomach, duodenum, jejunum, and ileum. Notes: Dissected tissue was thoroughly rinsed to remove unbound NCs and imaged by microscopy to detect tissue-associated fluorescent NCs.…”

“…39 We and others have shown that, upon intravenous administration in animal models, ICAM-1 targeting improves biodistribution of diagnostic and therapeutic agents. [40][41][42][43][44] Furthermore, ICAM-1-targeting NCs can be modulated to display optimal antibody surface density, size, and shape, leading to internalization into cells, which is suitable for intracellular drug transport. [45][46][47] In the context of drug delivery in the GI tract, however, ICAM-1 targeting has not been explored.…”