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 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.

Development of Novel Versatile Theranostic Platforms Based on Titanate Nanotubes: Towards Safe Nanocarriers for Biomedical Applications

“…One of the major challenges in radiation oncology is to get therapeutic effects in increasing the ionizing one while minimizing the administered doses whereas the dramatic side effects on healthy surrounding tissue should be minimized. TiONts are good candidates to induce a radiosensitizing effect (Mirjolet et al 2013(Mirjolet et al , 2017Loiseau et al 2019) -even though titanium has a low atomic number (Z = 22) (Maezawa et al 1996;Takakura 1996) -along with an absence of cytotoxicity (see section 4) (Mirjolet et al 2013;Papa et al 2013;Loiseau et al 2017). N. Millot et al studied the incubation of glioblastoma cell lines (SNB-19 and U87MG) with TiONts and under irradiation.…”

Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview

“…The high dose barrier can be mitigated if the drugs are designed to be more site-specific and more targeted as opposed to the current conventional intravenous (IV) delivery. For instance, targeted nanohybrids based on the titanate nanotubes incorporated with DCX showed enhanced cytotoxicity against human PC-3 prostate adenocarcinoma cells and less toxic than the free DCX in vitro [ 10 ]. Similarly, a cocktail administration of DCX and a photosensitizing agent incorporated in hyaluronic acid-coated nanoparticles improved the intracellular drug concentration with a concomitant slow-release inside the human breast cancer cells as compared to the free drug group treatment group [ 11 ].…”

Inclusion Complex of Docetaxel with Sulfobutyl Ether β-Cyclodextrin: Preparation, In Vitro Cytotoxicity and In Vivo Safety

“…In order to increase the solubility and effectively protect docetaxel from degradation, multiple coupling compounds or nanoparticles are often used as solubilizers and transporters. The proven docetaxel formulations include dendritic macromolecules [ 18 , 19 ], low molecular weight chitosan [ 20 , 21 , 22 ] C60 fullerenes [ 23 ], fat-based formulations [ 24 ] and gold nanoparticles [ 25 , 26 ]. Although there are optimizations for drug distribution and tumor killing efficiency in organisms, the inherent polydispersity of these systems affects their structure–activity relationships [ 27 , 28 , 29 ].…”