Synthesis and Grafting of Thioctic Acid−PEG−Folate Conjugates onto Au Nanoparticles for Selective Targeting of Folate Receptor-Positive Tumor Cells

Dixit, Vivek; Bossche, Johan Van den; Sherman, Debra M.; Thompson, David H.; Andres, R. P.

doi:10.1021/bc050335b

Cited by 265 publications

(173 citation statements)

References 36 publications

(36 reference statements)

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“…enzymes, receptors, antibodies, DNA) and cells, but they are also very attractive candidates for use as carriers in medical diagnosis and treatment. [7][8][9][10][11][12][13][14][15][16][17][18] Gold (Au) nanoparticles are well known for their surface plasmon resonance band (SPR), a phenomenon associated with coherent oscillations of conduction-band electrons on the nanoparticle surface upon interaction with light. 2,19 The wavelength of the SPR band depends from the chemical nature, size, shape and aggregation of the nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions

et al. 2013

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Au nanoparticles with diameters ranging between 15 and 170 nm have been synthesised in aqueous solution using a seed-mediated growth method, employing hydroxylamine hydrochloride as a reducing agent. Thiolated polyethylene glycol (mPEG-SH) polymers, with molecular weights ranging from 2100 to 51 000 g mol-1, were used as efficient particle stabilising ligands. Dynamic light scattering and zeta potential measurements confirmed that the overall mean diameter and zeta potential of the capped nanoparticles increased in a non-linear way with increasing molecular weight of the mPEG-SH ligand. Electron microscopy and thermal gravimetric analysis of the polymer-capped nanoparticles, with a mean gold core diameter of 15 nm, revealed that the grafting density of the mPEG-SH ligands decreased from 3.93 to 0.31 PEG nm-2 as the molecular weight of the ligands increased from 2100 to 51 400 g mol-1 respectively, due to increased steric hindrance and polymer conformational entropy with increase in the PEG chain length. Additionally, the number of bound mPEG-SH ligands, with a molecular weight of 10 800 g mol-1, was found to increase in a non-linear way from 278 (σ = 42) to approximately 12 960 PEG (σ = 1227) when the mean Au core diameter increased from 15 to 115 nm respectively. However, the grafting density of mPEG10 000-SH ligands was higher on 15 nm Au nanoparticles and decreased slightly from 1.57 to 0.8 PEG nm-2 when the diameter increased; this effect can be attributed to the fact that smaller particles offer higher surface curvature, therefore allowing increased polymer loading per nm2. Au nanoparticles were also shown to interact with CT-26 cells without causing noticeable toxicity

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Section: Introductionmentioning

confidence: 99%

PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions

et al. 2013

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“…These strategies include use of anti-FRα antibodies [10] or folic acid-conjugates to localize drugs [28][29][30], imaging compounds [31][32][33], T cells [34,35], nanoparticles [36], or oncolytic viruses [37] to FRα-expressing tumors. Besides these efforts, we have recently shown that FRα may have potential as a target for immunotherapeutic approaches in ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Kalli¹,

Oberg²,

Keeney³

et al. 2008

Gynecologic Oncology

369

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Objectives-Folate receptor α (FRα) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRα expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.Methods-FRα expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRα staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.Results-FRα expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRα status detected at diagnosis. Metastatic foci were similar to primary tumors in FRα staining. FRα status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.Conclusion-FRα expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRα expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.

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“…[117] For cancer therapy, folic acid (FA) or methotrexate (MTX) can be anchored onto nanoparticles for recognition by folate receptors, which are overexpressed on surfaces of many cancer cells. FA-grafted gold nanoparticles [118] or iron oxide [119] nanoparticles are specifically uptake by folate receptor-positive KB cells. Methotrexate provides an additional advantage as it can serve as a targeting ligand as well as a chemotherapeutic drug.…”

Section: In Vivo Targeting Of Nanoparticlesmentioning

confidence: 99%