Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts

Konda, Sreenivas; Aref, Michael; Wang, Steven; Brechbiel, Martin W.; Wiener, Erik C.

doi:10.1007/bf02668091

Cited by 175 publications

(81 citation statements)

References 36 publications

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“…In tumor imaging, antibody-SPIO conjugates were able to be used to successfully image numerous surface markers overexpressed in tumor vessels and cells, such transferrin receptor [115], folic acid receptor [116], VEGF [117], RGD [118], α ν β 3 -integrin as angiogenesis marker [119], Her2/neu (cerb B-2) tyrosinase receptor [114], uMUC-1 [120], LHRH-R [121], EGFR [122], CEA [123], CEACAM5 ( • " Fig. 5) [124], CXCR4 [125], CD20 [126] or B220 + (B-cell lymphomas) [127] with the help of T2w or T2*w MRI.…”

Section: Tumor Imagingmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Ittrich¹,

Peldschus²,

Raabe³

et al. 2013

Fortschr Röntgenstr

123

101

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Superparamagnetic iron oxide nanoparticles (SPIO) can be used to image physiological processes and anatomical, cellular and molecular changes in diseases. The clinical applications range from the imaging of tumors and metastases in the liver, spleen and bone marrow, the imaging of lymph nodes and the CNS, MRA and perfusion imaging to atherosclerotic plaque and thrombosis imaging. New experimental approaches in molecular imaging describe undirected SPIO trapping (passive targeting) in inflammation, tumors and associated macrophages as well as the directed accumulation of SPIO ligands (active targeting) in tumor endothelia and tumor cells, areas of apoptosis, infarction, inflammation and degeneration in cardiovascular and neurological diseases, in atherosclerotic plaques or thrombi. The labeling of stem or immune cells allows the visualization of cell therapies or transplant rejections. The coupling of SPIO to ligands, radio- and/or chemotherapeutics, embedding in carrier systems or activatable smart sensor probes and their externally controlled focusing (physical targeting) enable molecular tumor therapies or the imaging of metabolic and enzymatic processes. Monodisperse SPIO with defined physicochemical and pharmacodynamic properties may improve SPIO-based MRI in the future and as targeted probes in diagnostic magnetic resonance (DMR) using chip-based ?NMR may significantly expand the spectrum of in vitro analysis methods for biomarker, pathogens and tumor cells. Magnetic particle imaging (MPI) as a new imaging modality offers new applications for SPIO in cardiovascular, oncological, cellular and molecular diagnostics and therapy. Key Points: Citation Format:

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Section: Tumor Imagingmentioning

confidence: 99%

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Ittrich¹,

Peldschus²,

Raabe³

et al. 2013

Fortschr Röntgenstr

123

101

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“…gadomers) have been further explored alone, 8-10 conjugated to avidin/biotin, 11 conjugated to monoclonal antibodies, 12 or targeted to high-affinity folate receptors. 13 Shukla and co-workers evaluated a non-MRI-based, fluorescently labeled generation 5 PAMAM dendrimer modified with doubly-cyclized RGD peptides containing two disulfide linkages via four cysteine residues. 14 Langereis and co-workers reported the synthesis of a Gd(III)-DTPA-functionalized dendritic contrast agent modified with a cyclic NGR sequence to encourage preferential binding to tumor vasculature.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Biological Evaluation of Integrin α_vβ₃-Targeted PAMAM Dendrimers

et al. 2008

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Ligand size and valency strongly influence the receptor uptake and clearance of tumor angiogenesis imaging agents. The structures of successful imaging agents exhibit a high degree of variability, encompassing small mono-valent arginine-glycine-aspartic acid (RGD)-containing peptides, multivalent RGD-oligomers, and a monoclonal antibody against integrin alpha-v-beta-3 (α v β 3 ). We have pursued a nano-scale approach to imaging of angiogenesis using rationally designed polyamidoamine (PAMAM) dendrimers covalently adorned with RGD-cyclopeptides. An orthogonal oxime-ligation strategy was applied to chemoselectively effect conjugation of the PAMAM dendrimers with RGD-cyclopeptides for targeting α v β 3 . Fluorescent dyes for optical imaging and chelates for gadolinium-based magnetic resonance (MR) imaging were subsequently appended to create robust multimodal macromolecular imaging agents. Fluorescence microscopy revealed selective binding of the resulting RGD peptide-bearing dendrimer with empty chelates to α v β 3 -expressing cells, but somewhat reduced selectivity was observed following Gd(III) complexation. The expected incomplete saturation of chelates with Gd(III) ions permitted radiometal complexation, and an in vivo tissue distribution of the resulting agent in M21 melanoma tumorbearing mice showed mostly renal and reticuloendothelial accumulation, with the tumor:blood ratio peaking (3.30 ± .03) at 2 hr post-injection.

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“…25 So far, some papers regarding folate-appended dendrimers have been published. For example, Konda et al 26 reported the novel folate dendrimer magnetic resonance imaging contrast agents to the high affinity FR expressed in ovarian tumor xenografts. Shukla et al 27 demonstrated the FR-targeted boronated dendrimers as potential agents for neutron capture therapy.…”

Section: Introductionmentioning

confidence: 99%

Potential use of folate-polyethylene glycol (PEG)-appended dendrimer (G3) conjugate with α-cyclodextrin as DNA carriers to tumor cells

et al. 2012

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We previously reported that polyamidoamine STARBURST dendrimer (generation 3, G3) (dendrimer) conjugate with a-cyclodextrin (a-CyD) having an average degree of substitution of 2.4 of a-CyD (a-CDE) provided remarkable aspects as novel carriers for DNA and small-interfering RNA. To develop novel a-CDE derivatives with tumor cell specificity, we prepared folate-appended a-CDEs (Fol-a-CDEs) and folate-polyethylene glycol (PEG)-appended a-CDEs (Fol-PaCs) with the various degrees of substitution of folate (DSF), and evaluated in vitro and in vivo gene transfer activity, cytotoxicity, cellular association and physicochemical properties. In vitro gene transfer activity of Fol-a-CDEs (G3, DSF 2, 5 or 7) was lower than that of a-CDE (G3) in KB cells, folate receptor (FR)-overexpressing cancer cells. Of the three Fol-PaCs (G3, DSF 2, 5 or 7), Fol-PaC (G3, DSF 5) had the highest gene transfer activity in KB cells. The activity of Fol-PaC (G3, DSF 5) was significantly higher than that of a-CDE (G3) in KB cells, but not in A549 cells, FR-negative cells. Negligible cytotoxicity of the plasmid DNA (pDNA) complex with Fol-PaC (G3, DSF 5) was observed in KB cells or A549 cells up to a charge ratio of 100/1 (carrier/pDNA). The cellular association of the pDNA complex with Fol-PaC (G3, DSF 5) could be mediated by FR on KB cells, resulting in its efficient cellular uptake. Fol-PaC (G3, DSF 5) had a higher binding affinity with folate-binding protein than a-CDE (G3), although the physicochemical properties of pDNA complex with Fol-PaC (G3, DSF 5) were almost comparable to that with a-CDE (G3), although the onset charge ratio and the compaction ability of Fol-PaC (G3, DSF 5) were slightly different. Fol-PaC (G3, DSF 5) tended to show a higher gene transfer activity than a-CDE (G3) 12 h after intratumoral administration in mice. These results suggest that Fol-PaC (G3, DSF 5), not Fol-a-CDEs, could be potentially used as a FR-overexpressing cancer cell-selective DNA carrier.

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Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts

Cited by 175 publications

References 36 publications

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Synthesis, Characterization, and Biological Evaluation of Integrin α_vβ₃-Targeted PAMAM Dendrimers

Potential use of folate-polyethylene glycol (PEG)-appended dendrimer (G3) conjugate with α-cyclodextrin as DNA carriers to tumor cells

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Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts

Cited by 175 publications

References 36 publications

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Synthesis, Characterization, and Biological Evaluation of Integrin αvβ3-Targeted PAMAM Dendrimers

Potential use of folate-polyethylene glycol (PEG)-appended dendrimer (G3) conjugate with α-cyclodextrin as DNA carriers to tumor cells

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Synthesis, Characterization, and Biological Evaluation of Integrin α_vβ₃-Targeted PAMAM Dendrimers