Optimizing endothelial targeting by modulating the antibody density and particle concentration of anti-ICAM coated carriers

Calderón, Andrés J.; Bhowmick, Tridib Kumar; Leferovich, John; Burman, Bharat; Pichette, Benjamin; Muzykantov, Vladimir R.; Eckmann, David M.; Muro, Silvia

doi:10.1016/j.jconrel.2010.10.025

Cited by 69 publications

(100 citation statements)

References 45 publications

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“…Specifically, previous studies showed that a high dose of ICAM-mAb-coated particles (>1 × 10 12 particles per animal) may lead to up to 200% ID/g accumulation in lungs. Although the doses used in the current study (5.0 × 10 9 to 5.0 × 10 11 particles per animal) were not as high, they did confirm the dose dependence reported in the literature (51).…”

Section: Discussionsupporting

confidence: 83%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

563

507

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Vascular endothelium offers a variety of therapeutic targets for the treatment of cancer, cardiovascular diseases, inflammation, and oxidative stress. Significant research has been focused on developing agents to target the endothelium in diseased tissues. This includes identification of antibodies against adhesion molecules and neovascular expression markers or peptides discovered using phage display. Such targeting molecules also have been used to deliver nanoparticles to the endothelium of the diseased tissue. Here we report, based on in vitro and in vivo studies, that the specificity of endothelial targeting can be enhanced further by engineering the shape of ligand-displaying nanoparticles. In vitro studies performed using microfluidic systems that mimic the vasculature (synthetic microvascular networks) showed that rodshaped nanoparticles exhibit higher specific and lower nonspecific accumulation under flow at the target compared with their spherical counterparts. Mathematical modeling of particle-surface interactions suggests that the higher avidity and specificity of nanorods originate from the balance of polyvalent interactions that favor adhesion and entropic losses as well as shear-induced detachment that reduce binding. In vivo experiments in mice confirmed that shape-induced enhancement of vascular targeting is also observed under physiological conditions in lungs and brain for nanoparticles displaying anti-intracellular adhesion molecule 1 and anti-transferrin receptor antibodies.biodistribution | morphology | SMN | cylinder | drug delivery

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Section: Discussionsupporting

confidence: 83%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

563

507

View full text Add to dashboard Cite

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“…Immunofluorescence images showed increased fluorescence signals of LPS-induced EAs compared with resting EAs, which proved the up-regulated expression of ICAM-1 on EAs surface after LPS stimulation ( Figure 5A). The results suggested the establishment of pathological endothelium with over-expressed ICAM-1 in vitro (Calderon et al, 2011). Figure 5(B) exhibited obvious difference of mean fluorescence intensity (MFIs) between the cells incubated with anti-ICAM/SV/NLCs (182) and control IgG/SV/NLCs (138), which indicated higher uptake of anti-ICAM/SV/NLCs compared with their non-targeted counterparts.…”

Section: Cellular Uptake Study Of Icam-1 Antibody-conjugated Nlcsmentioning

confidence: 94%

“…The bio-distribution of anti-ICAM/SV/NLCs was evaluated in healthy mice, sham-operated mice, and LPS-challenged mice known with increased ICAM-1 expression (Calderon et al, 2011). which was likely due to the up-regulated ICAM-1 expression or the EPR effect in inflammation foci (Howard et al, 2014), given the potential inflammation triggered by surgery.…”

Section: Preparation Characterization and In Vivo Distribution Of Icmentioning

confidence: 99%

Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy

Wang

et al. 2017

Drug Delivery

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Acute lung injury (ALI) is a critical illness without effective therapeutic modalities currently. Recent studies indicated potential efficacy of statins for ALI, while high-dose statins was suggested to be significant for attenuating inflammation in vivo. Therefore, a lung-targeted drug delivery system (DDS) delivering simvastatin (SV) for ALI therapy was developed, attempting to improve the disease with a decreased dose and minimize potential adverse effects. SV-loaded nanostructured lipid carriers (SV/NLCs) with different size were prepared primarily. With particle size increasing from 143.7 nm to 337.8 nm, SV/NLCs showed increasing drug-encapsulated efficiency from 66.70% to 91.04%. Although larger SV/NLCs exhibited slower in vitro cellular uptake by human vascular endothelial cell line EAhy926 at initial stage, while in vivo distribution demonstrated higher pulmonary accumulation of the larger ones. Thus, the largest size SV/NLCs (337.8 nm) were conjugated with intercellular adhesion molecule 1 (ICAM-1) antibody (anti-ICAM/SV/NLCs) for lung-targeted study. The anti-ICAM/SV/NLCs exhibited ideal lung-targeted characteristic in lipopolysaccharide-induced ALI mice. In vivo i.v. administration of anti-ICAM/SV/NLCs attenuated TNF-a, IL-6 and inflammatory cells infiltration more effectively than free SV or non-targeted SV/NLCs after 48-h administration. Significant histological improvements by anti-ICAM/SV/NLCs were further revealed by H&E stain. Therefore, ICAM-1 antibody-conjugated NLCs may represent a potential lung-targeted DDS contributing to ALI therapy by statins.

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“…However, antibody-coated NCs display targeting and biodistribution patterns different from free antibodies due to differences in size and valency (which determines avidity), among other parameters. 45,51 We therefore assessed the biodistribution of IgG-coated polymer NCs in the GI tract of mice, compared to that of free IgG. A detailed characterization of IgG NCs, compared to uncoated NCs, is provided in Table 1.…”

Section: Biodistribution and Degradation Of Iggcoated Nanocarriers Inmentioning

confidence: 99%

“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Mane¹,

Muro²

2012

IJN

Self Cite

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Drug delivery to the gastrointestinal (GI) tract is key for improving treatment of GI maladies, developing oral vaccines, and facilitating drug transport into circulation. However, delivery of formulations to the GI tract is hindered by pH changes, degradative enzymes, mucus, and peristalsis, leading to poor GI retention. Targeting may prolong residence of therapeutics in the GI tract and enhance their interaction with this tissue, improving such aspects. We evaluated nanocarrier (NC) and ligand-mediated targeting in the GI tract following gastric gavage in mice. We compared GI biodistribution, degradation, and endocytosis between control antibodies and antibodies targeting the cell surface determinant intercellular adhesion molecule 1 (ICAM-1), expressed on GI epithelium and other cell types. These antibodies were administered either as free entities or coated onto polymer NCs. Fluorescence and radioisotope tracing showed proximal accumulation, with preferential retention in the stomach, jejunum, and ileum; and minimal presence in the duodenum, cecum, and colon by 1 hour after administration. Upstream (gastric) retention was enhanced in NC formulations, with decreased downstream (jejunal) accumulation. Of the total dose delivered to the GI tract, ∼60% was susceptible to enzymatic (but not pHmediated) degradation, verified both in vitro and in vivo. Attenuation of peristalsis by sedation increased upstream retention (stomach, duodenum, and jejunum). Conversely, alkaline NaHCO 3 , which enhances GI transit by decreasing mucosal viscosity, favored downstream (ileal) passage. This suggests passive transit through the GI tract, governed by mucoadhesion and peristalsis. In contrast, both free anti-ICAM and anti-ICAM NCs demonstrated significantly enhanced upstream (stomach and duodenum) retention when compared to control IgG counterparts, suggesting GI targeting. This was validated by transmission electron microscopy and energy dispersive X-ray spectroscopy, which revealed anti-ICAM NCs in vesicular compartments within duodenal epithelial cells. These results will guide future work aimed at improving intraoral delivery of targeted therapeutics for the treatment of GI pathologies.

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Optimizing endothelial targeting by modulating the antibody density and particle concentration of anti-ICAM coated carriers

Cited by 69 publications

References 45 publications

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy

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

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