Hydroxyapatite-binding micelles for the detection of vascular calcification in atherosclerosis

Chin, Deborah; Wang, Jonathan; Fontenay, Margot Mel de; Plotkin, Anastasia; Magee, Gregory A.; Chung, Eun Ji

doi:10.1039/c9tb01918a

Cited by 24 publications

(20 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For monocytes, cell viability from 1 to 100 µм concentrations of particles on monocytes remained above 80%, although some differences were seen between MCP‐1 PAMs and Col‐1 PAMs, Gd PAMs, and SCG PAMs at 100 µм, with a slightly lower viability observed for the latter three particle formulations. Nonetheless, overall, MCG PAMs and SCG PAMs were found to have minimal cytotoxic effects on hASMCs or monocytes (Figure 1D,E), similar to previous PAM reports from our group …”

Section: Resultssupporting

confidence: 90%

“…Nanoparticles have become favorable platforms for molecular imaging and targeted therapy. Previously, we have developed PAMs as tunable nanoparticles for targeted drug carriers and diagnostic agents . PAMs are comprised of peptide amphiphile (PA) molecules, consisting of a hydrophobic lipid tail attached to a hydrophilic headgroup, that self‐assemble into micelles.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, we have developed PAMs as tunable nanoparticles for targeted drug carriers and diagnostic agents. [30,[33][34][35] PAMs are comprised of peptide amphiphile (PA) molecules, consisting of a hydrophobic lipid tail attached to a hydrophilic headgroup, that self-assemble into micelles. Multimodal theranostic MCG PAMs for targeted therapy and diagnostics of atherosclerotic plaques were developed using MCP-1 peptides for CCR2 targeting, therapeutic Col-1 peptides for competitive inhibition of collagenases, and Gd contrast agents for MR imaging.…”

Section: Particle Synthesis and Characterizationmentioning

confidence: 99%

“…Previous studies on permeable arterial endothelium in atherosclerosis reported leaky endothelial tight junctions to be ≈20-1330 nm range. [34,[36][37][38] Given that MCG PAMs are smaller than 20 nm, our micelles have the capacity to extravasate past dysfunctional endothelium, allowing for passive targeting of plaques in addition to active targeting via the CCR2 receptor. [39] The zeta potential of 100 µм MCG PAMs in MQ water was found to be slightly positive (3.6 ± 2.1 mV), which is attributed to the net five positive charges of the MCP-1 peptide derived from the arginine and lysine residues.…”

Section: Particle Synthesis and Characterizationmentioning

confidence: 99%

“…Nonetheless, overall, MCG PAMs and SCG PAMs were found to have minimal cytotoxic effects on hASMCs or monocytes ( Figure 1D,E), similar to previous PAM reports from our group. [33,34,46] To confirm CCR2 targeting, Cy7-labeled MCG PAM or SCG PAM (100 µм) binding on hASMCs was evaluated after 1 h of incubation using fluorescence microscopy. When compared with the nontargeting SCG PAMs that lack the CCR2 binding motif, MCG PAMs showed significant binding to hASMCs ( Figure 1F).…”

Section: Particle Synthesis and Characterizationmentioning

confidence: 99%

See 4 more Smart Citations

Collagenase‐Cleavable Peptide Amphiphile Micelles as a Novel Theranostic Strategy in Atherosclerosis

Chin

Poon

Trac

et al. 2020

Advanced Therapeutics

Self Cite

View full text Add to dashboard Cite

Atherosclerosis is an inflammatory disease characterized by plaques that can cause sudden myocardial infarction upon rupture. Such rupture‐prone plaques have thin fibrous caps due to collagenase degradation, and a noninvasive diagnostic tool and targeted therapy that can identify and treat vulnerable plaques and may inhibit the onset of acute cardiac events. Toward this goal, monocyte‐binding, collagenase‐inhibiting, and gadolinium‐modified peptide amphiphile micelles (MCG PAMs) are developed. Monocyte chemoattractant protein‐1 (MCP‐1) binds to C‐C chemokine receptor‐2 expressed on pathological cell types present within plaques. Through the peptide binding motif of MCP‐1, MCG PAMs bind to monocytes and vascular smooth muscle cells in vitro. Moreover, using magnetic resonance imaging, MCG PAMs show enhanced targeting and successful detection of plaques in diseased mice in vivo and act as contrast agents for molecular imaging. Through the collagenase‐cleaving peptide sequence of collagen [VPMS‐MRGG], MCG PAMs can compete for collagenases that degrade the fibrous cap of plaques, providing therapy. MCG PAM‐treated mice show increased fibrous cap thickness by 61% and 113% histologically compared to nontargeting micelle‐ or PBS‐treated mice (p = 0.0075 and 0.001, respectively). Overall, this novel multimodal nanoparticle offers new theranostic opportunities for noninvasive diagnosis and treatment of atherosclerotic plaques.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Particle Synthesis and Characterizationmentioning

confidence: 99%

Section: Particle Synthesis and Characterizationmentioning

confidence: 99%

Section: Particle Synthesis and Characterizationmentioning

confidence: 99%

See 3 more Smart Citations

Collagenase‐Cleavable Peptide Amphiphile Micelles as a Novel Theranostic Strategy in Atherosclerosis

Chin

Poon

Trac

et al. 2020

Advanced Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

The Janus Nature of Nanohydroxyapatite in Tumor Progression

Shen

Wan

et al. 2021

Adv Funct Materials

View full text Add to dashboard Cite

Nanohydroxyapatite (nHAP) has broad applications because of its nanoscopical dimension, large specific surface area, biocompatibility, and low cytotoxicity. Researchers recently discovered that nHAP synthesized in vitro inhibits the growth of different types of tumor cells. Nanohydroxyapatite with potent drug adsorption and loading capacity has potential applications in tumor diagnosis and treatment. Because local tumors and areas of tumor metastasis also produce pathological nHAP in vivo to promote progression and invasion, the role of nHAP in tumorigenesis and development is perceived literature by many as Janus, the double‐faced deity in ancient Roman mythology. In the present review, two types of nHAP (those synthesized in vitro and those produced in vivo) that are affiliated with tumors, their mechanisms in tumor progression as well as their applications in tumor treatment are elucidated to create a backdrop for future research in this exciting, yet controversial arena.

show abstract

The effect of size, charge, and peptide ligand length on kidney targeting by small, organic nanoparticles

Huang

Jiang

Zhang

et al. 2020

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

Chronic kidney disease (CKD) affects 15% of the US adult population. However, most clinically available drugs for CKD show low bioavailability to the kidneys and non-specific uptake by other organs which results in adverse side effects. Hence, a targeted, drug delivery strategy to enhance kidney drug delivery is highly desired. Recently, our group developed small, organic nanoparticles called peptide amphiphile micelles (PAM) functionalized with the zwitterionic peptide ligand, (KKEEE) 3 K, that passage through the glomerular filtration barrier for kidney accumulation. Despite high bioavailability to the kidneys, these micelles also accumulated in the liver to a similar extent. To further optimize the physicochemical properties and develop design rules for kidney-targeting micelles, we synthesized a library of PAMs of varying size, charge, and peptide repeats. Specifically, variations of the original (KKEEE) 3 K peptide including (KKEEE) 2 K, (KKEEE)K, (EEKKK) 3 E, (EEKKK) 2 E, (EEKKK)E, KKKKK, and EEEEE were functionalized onto nanoparticles, and peptide surface density and PEG linker molecular weight were altered. After characterization with transmission electron microscopy (TEM) and dynamic light scattering (DLS), nanoparticles were intravenously administered into wildtype mice, and biodistribution was assessed through ex vivo imaging. All micelles localized to the kidneys, but nanoparticles that are positively-charged, close to the renal filtration size cutoff , and consisted of additional zwitterionic peptide sequences generally showed higher renal accumulation. Upon immunohistochemistry, micelles were confirmed to bind to the multiligand receptor, megalin, and histological analyses showed no tissue damage. Our study provides insight into the design of micelle carriers for kidney targeting and their potential for future therapeutic application.

show abstract

Hydroxyapatite-binding micelles for the detection of vascular calcification in atherosclerosis

Abstract: Hydroxyapatite-binding micelles show potential as vascular calcification diagnostic probes in atherosclerotic murine models and diseased human arteries ex vivo.

Cited by 24 publications

References 49 publications

Collagenase‐Cleavable Peptide Amphiphile Micelles as a Novel Theranostic Strategy in Atherosclerosis

Collagenase‐Cleavable Peptide Amphiphile Micelles as a Novel Theranostic Strategy in Atherosclerosis

The Janus Nature of Nanohydroxyapatite in Tumor Progression

The effect of size, charge, and peptide ligand length on kidney targeting by small, organic nanoparticles

Contact Info

Product

Resources

About