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Radiochemistry of Therapeutic Radionuclides
Published in David M. Goldenberg, Cancer Therapy with Radiolabeled Antibodies, 1995
There has been some interest in the use of MoAb conjugates of 105Rh103–105 for RAIT. A bifunctional chelate, 1,7-bis(2-hydroxybenzyl)-4-(p-aminobenzyl)diethylenetriamine (Bhabdt) (Figure 4), has been synthesized, complexed with 105Rh, activated to the corresponding isothiocyanate derivative, and conjugated to MoAb. Overall incorporation yields of 105Rh were 67%. 109Pd was first suggested as a suitable isotope for RAIT some time ago,106 and the bifunctional ligand, 6-(5-carboxypentyl)-5,7-dioxo-1,4,7,11-tetraazaundecane (Figure 4) was developed to give a neutral inert complex with Pd(II). The complex was shown to be stable to EDTA challenge, but serum stability studies were not performed. More recent work has described a hydrazinephosphine ligand (PhP(S)[N(Me)NH2]N(Me)NR2, where R can contain a carboxyl group for MoAb conjugation), which can be labeled with 109Pd in 15 min at 25°C in 90% yield.107111Ag has attractive radiophysical features for RAIT, with a 7-day half-life and medium-energy β-emission (Table 1). It has now been prepared in high purity,108 and is a promising potential RAIT isotope. 194Ir is a high energy β-emitter which has the advantage of being available from a generator system,109 the recent development of which may spur MoAb labeling work with this isotope.199Au has recently been prepared in a non-carrier-added form for use in gold cluster-labeled antibodies,110 whereby clusters of 11 gold atoms111 have been stabilized by seven derivatized triphenylphosphine atoms. For attachment to MoAbs, one triphenylphosphine p-phenyl carboxylate group was modified into a maleimide. The (199Au)11-cluster-maleimide could be conjugated to MoAbs and fragments containing free thiol groups in as little as 2 h. The (199Au)11-labeled 17-1A MoAb was tested in vivo and the fragments, particularly, showed higher kidney uptake than the corresponding MoAb radiolabeled with 111In.
Organotypic and primary neural cultures as models to assess effects of different gold nanostructures on glia and neurons
Published in Nanotoxicology, 2019
Jeff Ji, Alexandre Moquin, Franck Bertorelle, Philip KY Chang, Rodolphe Antoine, Julia Luo, R. Anne McKinney, Dusica Maysinger
Au15(SG)13 were synthesized as reported (Russier-Antoine et al. 2014). The monodispersity in terms of gold cluster sizes was verified by ESI-mass spectrometry (Hamouda et al. 2013). An ESI mass spectrum for the protected Au15 cluster from solution, acquired under gentle ESI conditions is shown in Figure S1. A charge state distribution was observed from [M+5H+]5+ through [M+7H+]7+. Deconvolution of charge states from 5+ through 7+, provided a mass of 6 937Da for the intact Au cluster, consistent with the calculated mass of Au15(SG)13. The linear optical absorption spectrum (see Figure S1) of Au15(SG)13 is composed by a shoulder band at ∼370nm, and the energy gap is determined to be ∼2.5eV (at zero absorbance). Photoluminescence quantum yields are low in aqueous solutions, typically lower than 0.4 %. Size determination of Au15(SG)13 clusters indicates a diameter of 1.6nm and a hydrodynamic diameter of 2.9nm (Soleilhac et al. 2017). Au-nanoclusters coated with CTAB could not be prepared as the force between thiol groups of GSH and Au atoms are dative bonds which are stronger (ca. 1 nN) (Xue et al. 2014) compared to the non-covalent surfactant-coating of the gold structures and the CTAB molecules.
Anti-biofilm effects of gold and silver nanoparticles synthesized by the Rhodiola rosea rhizome extracts
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Priyanka Singh, Santosh Pandit, Mariam Beshay, V.R.S.S. Mokkapati, Jørgen Garnaes, Mikael Emil Olsson, Abida Sultan, Aiga Mackevica, Ramona Valentina Mateiu, Henrik Lütken, Anders Egede Daugaard, Anders Baun, Ivan Mijakovic
The synthesized nanoparticles were analyzed by MALDI-TOF to map the composition of the capping layer. Both AuNP and AgNP samples produced ions in the low-mass regions of the spectra between 500 and 22,000 m/z. For AuNPs, several peaks were found to correspond to gold cluster ions (197Au+, atomic weight 196.9666 u), including 197Au3+ (calculated value 590.8997), 197Au4+ (787.8663), 197Au5+ (984.8328), 197Au6+ (1181.7993), 197Au7+ (1378.7659), 197Au8+ (1575.7325) and 197Au12+ (2363.5992). These are indicated in acquired spectra shown in (Figure 3(A)). For AgNPs, several peaks could be assigned to silver cluster ions (107Ag+, atomic weight 107.8682 u), in particular of higher cationic species, such as 107Ag6+ (calculated value 647.2092), 107Ag7+ (755.0774), 107Ag8+ (862.9456), 107Ag9+ (970.8138), 107Ag11+ (1186.5502), 107Ag13+ (1402.2866), 107Ag15+ (1618.023), 107Ag17+ (1833.7594) and 107Ag19+ (2049.4958) (Figure 3(B)). Although a more detailed investigation is required to answer all the biological components present on the surface, this study provides the basic understanding of capping layer content [23].
Mesoporous silica nanoparticles: synthesis, classification, drug loading, pharmacokinetics, biocompatibility, and application in drug delivery
Published in Expert Opinion on Drug Delivery, 2019
Zhe Li, Yongtai Zhang, Nianping Feng
The pH-responsive DDS is one of the most explored controlled DDS for the treatment of cancer [140]. In normal tissues and blood, the pH is 7.2 and 7.5, respectively; however, in the tumor microenvironment, the pH is between 6.0 and 7.0 [141,145]. Therefore, the pH gradients provide opportunities for pH-responsive MSNs as controlled DDS for the treatment of cancer. By using polyelectrolytes, supramolecular nanovalves, pH-sensitive linkers, and acid-decomposable inorganic material, the triggered release of antineoplastics from MSNs could be achieved [141]. For pH-responsive drug delivery, polyelectrolyte (PAH/PSS) multilayer-coated hollow MSNs were prepared [146]. MSNs can also be modified with polyethyleneimine/cyclodextrin, carboxylic acid/polycations, and poly-(dimethyldiallylammonium) chloride for pH-responsive release [98]. Interestingly, it does not have to remove CTAB during the synthesis of MSNs. Because CTAB may have a synergistic effect with other drugs. As reported, the synthesized MSNs before removing CTAB (e.g. CTAB@MSNs) with a highly precise pH-responsive drug release behavior both in vitro and in vivo were constructed by the facile co-loading of anti-cancer drug and surfactant chemosensitizer into MSNs via a one-pot co-self-assembly strategy among the drugs, CTAB micelles, and silicon sources. The DDS also exhibited high drug efficiencies against both drug-sensitive MCF-7 cells and drug-resistant MCF-7/ADR cells by a synergistic cell cycle arrest/apoptosis-inducing effect between anti-cancer drug and surfactant chemosensitizer (CTAB) [145]. Moreover, a novel pH-responsive MSNs delivery system responsive to the endosomal acidification conditions was developed. The DDS with pH-responsive N-methylbenzimidazole (MBI) as stalk and β-cyclodextrin (β-CD) as the cap was responsive to the endosomal acidification conditions inTHP-1 and KB-31 cell lines. The MBI stalk with the optimized pKa endowed the nanovalves with the capability of binding the β-CD ring strongly at pH 7.4 and trapping drug molecules in the nanopores. The β-CD caps dissociated at pH <6, as in acidifying endosomal compartments, and then the drug released from the carrier [147]. Premature leakage of drugs is inevitable in many nanocarriers, including MSNs. To solve this problem, negatively charged gold cluster bovine serum albumin (BSA) nanogates electrostatically attached on ammonium-functionalized MSNs to effectively block the pores and provided a pH-responsive release and co-delivery of two different anticancer drugs, which led to less than 3% of drug leakage after one week thanks to the dense coating of BSA. In the meantime, BSA also reduced the immunotoxicity of MSNs [148]. Targeting can also be combined with pH-responsive controlled drug release. In a study, the targeting polymer PEG-FA on the surface of polydopamine (PDA)-modified MSNs (MSNs@PDA-PEG-FA) were developed with pH-sensitive PDA coating served as a gatekeeper and FA served as targeting ligand [149].