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Titanate Nanotubes Engineered with Gold Nanoparticles and Docetaxel to Enhance Radiotherapy on Xenografted Prostate Tumors.

ABSTRACT: Nanohybrids based on titanate nanotubes (TiONts) were developed to fight prostate cancer by intratumoral (IT) injection, and particular attention was paid to their step-by-step synthesis. TiONts were synthesized by a hydrothermal process. To develop the customengineered nanohybrids, the surface of TiONts was coated beforehand with a siloxane (APTES), and coupled with both dithiolated diethylenetriaminepentaacetic acidmodified gold nanoparticles (Au@DTDTPA NPs) and a heterobifunctional polymer (PEG3000) to significantly improve suspension stability and biocompatibility of TiONts for targeted biomedical applications. The prefunctionalized surface of this scaffold had reactive sites to graft therapeutic agents, such as docetaxel (DTX). This novel combination, aimed at retaining the AuNPs inside the tumor via TiONts, was able to enhance the radiation effect. Nanohybrids have been extensively characterized and were detectable by SPECT/CT imaging through grafted Au@DTDTPA NPs, radiolabeled with 111In. In vitro results showed that TiONtsAuNPsPEG3000DTX had a substantial cytotoxic activity on human PC3 prostate adenocarcinoma cells, unlike initial nanohybrids without DTX (Au@DTDTPA NPs and TiONtsAuNPsPEG3000). Biodistribution studies demonstrated that these novel nanocarriers, consisting of AuNP- and DTXgrafted TiONts, were retained within the tumor for at least 20 days on mice PC3 xenografted tumors after IT injection, delaying tumor growth upon irradiation.

SUBMITTER: Loiseau A

PROVIDER: S-EPMC6966691 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Titanate Nanotubes Engineered with Gold Nanoparticles and Docetaxel to Enhance Radiotherapy on Xenografted Prostate Tumors.

Loiseau Alexis A Boudon Julien J Oudot Alexandra A Moreau Mathieu M Boidot Romain R Chassagnon Rémi R Saïd Nasser Mohamed NM Roux Stéphane S Mirjolet Céline C Millot Nadine N

Cancers 20191206 12

Nanohybrids based on titanate nanotubes (TiONts) were developed to fight prostate cancer by intratumoral (IT) injection, and particular attention was paid to their step-by-step synthesis. TiONts were synthesized by a hydrothermal process. To develop the customengineered nanohybrids, the surface of TiONts was coated beforehand with a siloxane (APTES), and coupled with both dithiolated diethylenetriaminepentaacetic acidmodified gold nanoparticles (Au@DTDTPA NPs) and a heterobifunctional polymer (P ...[more]

PMID: 31817706

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Project description:BackgroundApplied nanomaterials in targeted drug delivery have received increased attention due to tangible advantages, including enhanced cell adhesion and internalization, controlled targeted release, convenient detection in the body, enhanced biodegradation, etc. Furthermore, conjugation of the biologically active ingredients with the drug-containing nanocarriers (nanobioconjugates) has realized impressive opportunities in targeted therapy. Among diverse nanostructures, halloysite nanotubes (NHTs) with a rolled multilayer structure offer great possibilities for drug encapsulation and controlled release. The presence of a strong hydrogen bond network between the rolled HNT layers enables the controlled release of the encapsulated drug molecules through the modulation of hydrogen bonding either in acidic conditions or at higher temperatures. The latter can be conveniently achieved through the photothermal effect via the incorporation of plasmonic nanoparticles.ResultsThe developed nanotherapeutic integrated natural halloysite nanotubes (HNTs) as a carrier; gold nanoparticles (AuNPs) for selective release; docetaxel (DTX) as a cytotoxic anticancer agent; human IgG1 sortilin 2D8-E3 monoclonal antibody (SORT) for selective targeting; and 3-chloropropyltrimethoxysilane as a linker for antibody attachment that also enhances the hydrophobicity of DTX@HNT/Au-SORT and minimizes DTX leaching in body's internal environment. HNTs efficiently store DTX at room temperature and release it at higher temperatures via disruption of interlayer hydrogen bonding. The role of the physical expansion and disruption of the interlayer hydrogen bonding in HNTs for the controlled DTX release has been studied by dynamic light scattering (DLS), electron microscopy (EM), and differential scanning calorimetry (DSC) at different pH conditions. HNT interlayer bond disruption has been confirmed to take place at a much lower temperature (44 °C) at low pH vs. 88 °C, at neutral pH thus enabling the effective drug release by DTX@HNT/Au-SORT through plasmonic photothermal therapy (PPTT) by light interaction with localized plasmon resonance (LSPR) of AuNPs incorporated into the HNT pores.ConclusionsSelective ovarian tumor targeting was accomplished, demonstrating practical efficiency of the designed nanocomposite therapeutic, DTX@HNT/Au-SORT. The antitumor activity of DTX@HNT/Au-SORT (apoptosis of 90 ± 0.3%) was confirmed by in vitro experiments using a caov-4 (ATCC HTB76) cell line (sortilin expression > 70%) that was successfully targeted by the sortilin 2D8-E3 mAb, tagged on the DTX@HNT/Au.

Dataset Information

Titanate Nanotubes Engineered with Gold Nanoparticles and Docetaxel to Enhance Radiotherapy on Xenografted Prostate Tumors.

Publications

Titanate Nanotubes Engineered with Gold Nanoparticles and Docetaxel to Enhance Radiotherapy on Xenografted Prostate Tumors.

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