Gold nanoparticle bioconjugates labelled with <sup>211</sup>At for targeted alpha therapy

Dziawer, L.; Koźmiński, Przemysław; Męczyńska-Wielgosz, Sylwia; Pruszyński, Marek; Lyczko, Monika; Wąs, Bogdan; Celichowski, Grzegorz; Grobelny, Jarosław; Jastrzȩbski, J.; Bilewicz, Aleksander

doi:10.1039/c7ra06376h

Cited by 49 publications

(58 citation statements)

References 35 publications

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“…The cytotoxicity of 225 Ac-silane-TiO 2 -PEG-SP(5-11) is very high in comparison to other radiopharmaceuticals including conjugates radiolabelled with α-emitters like 213 Bi or 211 At (Gadbois et al 1996 ; Dziawer et al 2017 ), however, it is comparable with other radiobioconjugates of 223 Ra and 225 Ac (Borchardt et al 2003 ; Piotrowska et al 2017 ). The decay processes of 225 Ac and 223 Ra include four α and two β − emissions to a stable 209 Bi and 207 Pb daughters.…”

Section: Resultsmentioning

confidence: 94%

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

et al. 2018

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The 225Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with 225Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work, we propose to apply TiO2 nanoparticles (NPs) as carrier for 225Ac and its decay products. The surface of TiO2 nanoparticles with 25 nm diameter was modified with Substance P (5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles functionalized with Substance P (5-11) were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). The obtained results show that one TiO2-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO2-PEG-SP(5-11) conjugates were labelled with 225Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO2 surface. The labelled bioconjugates almost quantitatively retain 225Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of 221Fr, a first decay daughter of 225Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized 225Ac-TiO2-PEG-SP(5-11) has shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours.

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Section: Resultsmentioning

confidence: 94%

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

et al. 2018

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“…Thus, direct sorption of 223 Ra onto surface or intrinsic labelling of nanocariers, e.g., nanohydroxyapatites, LaPO 4 , SPIONs and others was investigated [ 6 , 8 , 17 ]. Due to the problematic chemistry of 211 At several studies were focused on the possibility of trapping astatine into a nanoconstruct (e.g., gold or silver nanoparticles (NPs), 211 AtCl@US-tubes, TiO 2 ), attached to targeting vector via a linker [ 54 , 55 , 56 , 57 ]. Synthesized nanoconstructs might be stabilised with polyethyleneoxide or polyethylene glycol (PEG).…”

Section: General Radiopharmaceutical Issuesmentioning

confidence: 99%

“…The radiobioconjugates were stable for 24 h in human serum and cerebrospinal fluid, exhibiting high toxicity to glioma cancer cells. However, only local drug application, not intravenous injection, was recommended because of their relatively large size and high hydrophilicity [ 57 , 106 ].…”

Section: Vectors For Targeted Alpha Particle Therapymentioning

confidence: 99%

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

2018

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This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like 211At, 223Ra, 225Ac/213Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging. Special attention is given to the nuclear recoil effect and its impacts on the possible use of alpha emitters for cancer treatment, proper dose estimation, and labelling chemistry. The most recent and important achievements in the development of alpha emitters carrying vectors for preclinical and clinical use are highlighted along with an outlook for future developments.

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“…Other examples of gold theranostic nanoparticles are the 99m Tc/ 177 Lu 177 Lu‐radiolabelled Tat‐Bombesin targeting system, which has shown high levels of uptake by breast and prostate cancer cells, 41 the AuNPs targeting the breast cancer cells with 177 Lu‐labelled dendrimer (PAMAM‐G4)—folate and bombesin, 42 177 Lu‐trastuzumab modified AuNP nanoparticles targeting HER2‐overexpressing tumour cells, 43 the 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) chelators modified with 177 Lu‐PEG‐panitumumab tagged to AuNPs for triple negative breast tumour cells or locally advanced breast cancer cells, 44,45 and the 177 Lu‐labelled AuNPs conjugated to cyclo‐RGDfK(C) peptide for glioma therapeutics 46 . Similarly, gold nanoparticles functionalized with chlorotoxin peptide and entrapped with polyethylenimine have been developed for glioma imaging, 47 and a functionalization scheme with the peptide fragment P5‐11 for tagging 211 At to be used in alpha therapy has shown highly cytotoxic effects in glioma cells 48 . Further increase in radiosensitization of 103 Pd in cancer brachytherapy has been achieved by synthesizing Pd@Au–PEG nanoparticles 49 …”

Section: Different Nanoparticle Systems Used For Delivery Of Radiophamentioning

confidence: 99%

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties

Datta

Ray

2020

Labelled Comp Radiopharmac

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Application of nanotechnology principles in drug delivery has created opportunities for treatment of several diseases. Nanotechnology offers the advantage of overcoming the adverse biopharmaceutics or pharmacokinetic properties of drug molecules, to be determined by the transport properties of the particles themselves. Through the manipulation of size, shape, charge, and type of nanoparticle delivery system, variety of distribution profiles may be obtained. However, there still exists greater need to derive and standardize definitive structure property relationships for the distribution profiles of the delivery system. When applied to radiopharmaceuticals, the delivery systems assume greater significance. For the safety and efficacy of both diagnostics and therapeutic radiopharmaceuticals, selective localization in target tissue is even more important. At the same time, the synthesis and fabrication reactions of radiolabelled nanoparticles need to be completed in much shorter time. Moreover, the extensive understanding of the several interesting optical and magnetic properties of materials in nanoscale provides for achieving multiple objectives in nuclear medicine. This review discusses the various nanoparticle systems, which are applied for radionuclides and analyses the important bottlenecks that are required to be overcome for their more widespread clinical adaptation.

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Gold nanoparticle bioconjugates labelled with ²¹¹At for targeted alpha therapy

Abstract: Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Due to the relatively high availability,

Cited by 49 publications

References 35 publications

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties

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Gold nanoparticle bioconjugates labelled with 211At for targeted alpha therapy

Abstract: Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Due to the relatively high availability,

Cited by 49 publications

References 35 publications

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties

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Gold nanoparticle bioconjugates labelled with ²¹¹At for targeted alpha therapy