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 custom-engineered nanohybrids, the surface of TiONts was coated beforehand with a siloxane (APTES), and coupled with both dithiolated diethylenetriaminepentaacetic acid-modified gold nanoparticles (Au@DTDTPA NPs) and a heterobifunctional polymer (PEG3000) to significantly improve suspension stability and biocompatibility of TiONts for targeted biomedical applications. The pre-functionalized 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 TiONts-AuNPs-PEG3000-DTX had a substantial cytotoxic activity on human PC-3 prostate adenocarcinoma cells, unlike initial nanohybrids without DTX (Au@DTDTPA NPs and TiONts-AuNPs-PEG3000). Biodistribution studies demonstrated that these novel nanocarriers, consisting of AuNP- and DTX-grafted TiONts, were retained within the tumor for at least 20 days on mice PC-3 xenografted tumors after IT injection, delaying tumor growth upon irradiation.

Highlights

  • Cancer remains one of the world’s most devastating diseases with approximately 0.2% of people worldwide diagnosed with cancer at some point during their life [1]

  • This paper describes and analyzes each step required for the synthesis of a generation nanohybrid

  • an increasing interest to use gold nanoparticles (AuNPs) that did not seem to stick to each other and were relatively evenly diethylenetriaminepentaacetic acid bis(anhydride) (DTPA-BA), tetrachloroauric acid trihydrate distributed over the whole surface of TiONts

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Summary

Introduction

Cancer remains one of the world’s most devastating diseases with approximately 0.2% of people worldwide diagnosed with cancer at some point during their life [1]. In 2019 in the United States, prostate cancer was the third-most diagnosed cancer, with close to 175,000 estimated new cases, corresponding to 1 prostate cancer over 10 detected cancers, being the second leading cause of cancer-related deaths in men with more than. Anticancer chemotherapeutic agents such as docetaxel (DTX) are used to target tumor cells in prostate cancer treatment. DTX is an anti-mitotic chemotherapeutic agent, well known to decrease androgen receptor activation in castration-resistant prostate cancer cells [5,6]. It has been approved by Food and Drug Administration (FDA) in particular for the treatment of hormone-refractory prostate cancers [7]. Injected drugs weakly reach tumor sites, and patients who undergo repeated treatments develop drug resistance within 24 months of initial exposure [6,9,10]

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