Preparation and Long-Term Biodistribution Studies of a Pamam Dendrimer G5–Gd-BnDOTA Conjugate for Lymphatic Imaging

Opina, Ana Christina L.; Wong, Karen; Griffiths, Gary L.; Türkbey, Barış; Bernardo, Marcelino; Nakajima, Takahito; Kobayashi, Hisataka; Choyke, Peter L.; Vasalatiy, Olga

doi:10.2217/nnm.14.113

Cited by 34 publications

(18 citation statements)

References 49 publications

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“…The observation of the SAP and TSAP isomers using HPLC was reported in Gd-pSCN BnDOTA and Eu-pNO2-BnDOTA 32 , however this is the first report that studied the interconversion of isomers across the lanthanide series using HPLC. The use of different types of C18 columns and mobile phase conditions (with and without TFA) did not change the elution profile of the isomers.…”

Section: Resultsmentioning

confidence: 90%

Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies

et al. 2016

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A rigidified and symmetrical polymethylated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand bearing four SSSS methyl groups in both the tetraaza ring and the acetate arms (SSSS-SSSS-M4DOTMA) was prepared. The isomer ratio of SSSS-SSSS-M4DOTMA complexed with a series of lanthanide ions was carefully investigated using RP-HPLC and NMR. A square antiprismatic (SAP) configuration was exclusively observed for the early lanthanides, while the twisted square antiprismatic (TSAP) geometry was preferred as the lanthanide ion size decreases. The late lanthanides preferentially adopted the TSAP geometry. One of the pendant arms was modified with a pyridyl disulfide group (SSSS-SSSS-M8SPy) for cysteine attachment and displayed a similar isomer trend as the parent compound, Ln-SSSS-SSSS-M4DOTMA. Covalent attachment to the ubiquitin S57C mutant showed resonances whose intensities are in agreement with the isomeric population observed by HPLC. Furthermore, the NOE experiments combined with quantum chemical calculations have unequivocally demonstrated that the SAP of Pr-SSSS-SSSS-M4DOTMA and Pr-SSSS-SSSS-M8SPy, as well as the TSAP of Yb-SSSS-SSSS-M8SPy are more stable than their corresponding isomers.

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Section: Resultsmentioning

confidence: 90%

Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies

et al. 2016

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“…Dual contrast agents can be used to improve clinical diagnosis, since single modal signals can give false positive diagnosis of lesions due to background signals in neighbouring tissues. However, bioaccumulation of these dendrimer-conjugates in organs remains an issue, limiting their clinical applications [49].…”

Section: Imaging Agentsmentioning

confidence: 99%

PAMAM dendrimer - cell membrane interactions

Fox

Richardson

Briscoe

2018

Advances in Colloid and Interface Science

191

135

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. 2018 PAMAM dendrimers have been conjectured for a wide range of biomedical applications due to their tuneable physicochemical properties. However, their application has been hindered by uncertainties in their cytotoxicity, which is influenced by dendrimer generation (i.e. size and surface group density), surface chemistry, and dosage, as well as cell specificity. In this review, biomedical applications of polyamidoamine (PAMAM) dendrimers and some related cytotoxicity studies are first outlined. Alongside these in vitro experiments, lipid membranes such as supported lipid bilayers (SLBs), liposomes, and Langmuir monolayers have been used as cell membrane models to study PAMAM dendrimer-membrane interactions. Related experimental and theoretical studies are summarized, and the physical insights from these studies are discussed to shed light on the fundamental understanding of PAMAM dendrimer-cell membrane interactions. We conclude with a summary of some questions that call for further investigations.a b s t r a c t a r t i c l e i n f o Available online 27 June

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“…4,5 Generation 5 (G5) PAMAM dendrimers are the most promising scaffolds due to their spherical and flexible structure, well-defined molecular weight, fine size (approximately 5 nm), and proper amount of surface groups (128 branches) for the conjugation of therapeutics or diagnostic agents. 6 Recently, researchers found that low generation (G ≤ 4) dendrimers have certain bioactivities and functions.…”

Section: ■ Introductionmentioning

confidence: 99%

Protective Effects and Mechanisms of G5 PAMAM Dendrimers against Acute Pancreatitis Induced by Caerulein in Mice

et al. 2014

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In this study, generation 5 (G5) polyamidoamine (PAMAM) dendrimers with two different surface groups, G4.5-COOH and G5-OH, were investigated for their protective effects on pancreas injury in a caerulein-induced acute pancreatitis (AP) mouse model. Both dendrimers significantly decreased pathological changes in the pancreas and reduced the inflammatory infiltration of macrophages in pancreatic tissues. In addition, the expression of pro-inflammatory cytokines was significantly inhibited by the two dendrimers, not only in pancreatic tissues from AP mice but also in vitro in mouse peritoneal macrophages with LPS-induced inflammation. G4.5-COOH, which had better in vivo protective effects for AP than G5-OH, led to a significant reduction in the total number of plasma white blood cells (WBCs) and monocytes in AP mice, and its anti-inflammatory mechanism was related to inhibition of the nuclear translocation of NF-κB in macrophages.

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Preparation and Long-Term Biodistribution Studies of a Pamam Dendrimer G5–Gd-BnDOTA Conjugate for Lymphatic Imaging

Cited by 34 publications

References 49 publications

Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies

Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies

PAMAM dendrimer - cell membrane interactions

Protective Effects and Mechanisms of G5 PAMAM Dendrimers against Acute Pancreatitis Induced by Caerulein in Mice

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