Silica@zirconia@poly(malic acid) nanoparticles: promising nanocarriers for theranostic applications

L. Naszályi Nagy; A. Polyak; J. Mihály; Á. Szécsényi; I. Cs. Szigyártó; Zs. Czégény; E. Jakab; P. Németh; B. Magda; P. Szabó; Zs. Veres; K. Jemnitz; I. Bertóti; R. P. Jóba; Gy. Trencsényi; L. Balogh; A. Bóta

doi:10.1039/C6TB01102K

Silica@zirconia@poly(malic acid) nanoparticles: promising nanocarriers for theranostic applications†

L. Naszályi Nagy,

‡*^a A. Polyak,^bc J. Mihály,^a Á. Szécsényi,§^a I. Cs. Szigyártó,^a Zs. Czégény,^a E. Jakab,^a P. Németh,^a B. Magda,^d P. Szabó,^d Zs. Veres,^d K. Jemnitz,^d I. Bertóti,^a R. P. Jóba,^e Gy. Trencsényi,^f L. Balogh^b and A. Bóta^a

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* Corresponding authors

^a Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Magyar Tudósok Blvd 2, Budapest, Hungary
E-mail: nagy.naszalyi.livia@ttk.mta.hu
Tel: +36-1-382-6836

^b Department of Radiobiology, National Research Institute for Radiobiology and Radiohygiene, H-1221 Anna Str 5, Budapest, Hungary

^c Department of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str 1, D-30625, Hannover, Germany

^d Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1117 Magyar Tudósok Blvd 2, Budapest, Hungary

^e Department of Nuclear Medicine, Semmelweis University, H-1082 Üllői Rd 78, Budapest, Hungary

^f Department of Nuclear Medicine, University of Debrecen, H-4032 Nagyerdei Blvd 98, Debrecen, Hungary

Abstract

Silica@zirconia@poly(malic acid) nanocarriers of 110 nm mean diameter were designed, synthesized and characterized for the targeted delivery of diagnostic and therapeutic ^99mTc to folate-overexpressing tumors. An important achievement was that a multifunctional L-(−)-malic-acid-based copolymer was formed in situ at the surface of the inorganic cores in a single synthetic step incorporating L-(−)-malic acid, β-cyclodextrin rings, folic acid moieties, and polyethylene glycol chains. Morphological and in-depth structural analysis of the particles proved their core@shell structure. Stability experiments in aqueous media evidenced that stable suspensions can be obtained from the lyophilized powder in 10 mM phosphate buffer at pH 7.4. During 14-day degradation experiments, the nanoparticles were found to be slowly dissolving (including inorganic core) in saline and also in total cell medium. An in vitro toxicity assay on hepatocytes showed a concentration-dependent decrease of cell viability down to 63 ± 1% at the highest applied concentration (0.5 mg ml⁻¹). Proof of concept experiments of technetium-99m radiolabelling and in vivo labelling stability are presented.

Journal of Materials Chemistry B

Silica@zirconia@poly(malic acid) nanoparticles: promising nanocarriers for theranostic applications†

Abstract

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Silica@zirconia@poly(malic acid) nanoparticles: promising nanocarriers for theranostic applications

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