Biocompatible titanate nanotubes with high loading capacity of genistein: cytotoxicity study and anti-migratory effect on U87-MG cancer cell lines

Oudot

et al. 2019

Cancers

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.

Section: Introductionmentioning

confidence: 99%

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

Oudot

et al. 2019

Cancers

“…Tubular nanoparticles are more readily internalized than their spherical counterparts of a similar volume. [18b,20] This is why our group, and some others, are developing TiONts for a variety of biomedical applications, such as dopamine detection, transfection,[20a] imaging, when conjugated with superparamagnetic iron oxide nanoparticles, drug delivery, and cancer cell radiosensitization . Our group has previously studied the internalization of TiONts in various cell lines (cardiomyocytes,[20a] CHO, SNB19 and U87MG), in which TiONts did not induce cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

“…[21c,27,29] These modifications can also allow new functionalities to be added. [28b,30] To date, very few studies have investigated the functionalization of TiONts for biomedical applications: polyethylene glycol (PEG), polyethylene imine polymers or genistein have been grafted onto the surface of TiONts . Herein, TiONts were engineered as a theranostic nanoplatform since several molecules were grafted onto their surface for various purposes.…”

Section: Introductionmentioning

confidence: 99%

Taxane‐Grafted Metal‐Oxide Nanoparticles as a New Theranostic Tool against Cancer: The Promising Example of Docetaxel‐Functionalized Titanate Nanotubes on Prostate Tumors

Adv Healthcare Materials

Mirjolet

et al. 2017

The combination of anticancer drugs and metal oxide nanoparticles is of great interest in cancer nanomedicine. Here, the development of a new nanohybrid, titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are conjugated by covalent linkages. Unlike most nanoparticles currently being developed for biomedical purposes, TiONts present a needle-shaped morphology. The surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero-bifunctional polymer (polyethylene glycol) to create well-dispersed and biocompatible nanovectors. The prefunctionalized surface of this scaffold has valuable attachments to graft therapeutic agents (DTX in our case) as well as chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have demonstrated that the association between TiONts and DTX shows cytotoxic activity against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts without DTX do not. Finally, the first in vivo tests with intratumoral injections show that more than 70% of TiONts nanovectors are retained within the tumor for at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is significantly slower than that in mice receiving free DTX. This nanohybrid can thus become a promising new tool in biomedicine to fight against prostate cancer.

“…In 2016, T. Baati et al have shown the effectiveness of a TiONt-based nanocarrier against glioblastoma multiform with a controlled administration of genistein (biologically active flavonoid) in glioblastoma cells (Baati et al 2016). This study showed that these TiONts have a drug loading efficiency of 51.2 wt% and allows a controlled release of the therapeutic agent.…”

Section: Tionts As New Nanocarriersmentioning

confidence: 92%

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

Sallem

New Trends in Macromolecular and Supramolecular Chemistry for Biological Applications

et al. 2021

The concept of nanomaterials that can be designed and administered into the human body to improve health is of great interest. During the past years there has been an increasing amount of research on the uses of nanomaterials in diverse areas of biomedical research including biological sensing, labelling, imaging, cell separation and therapy. In this chapter, the first evaluation of titanate nanotubes (TiONts) as potential carriers of therapeutic molecules is presented. TiONts with controlled parameters have been developed from a hydrothermal synthesis and their biomedical applications have been explored over the last decade. These nanotubes are elaborated as stable suspensions of nanocarriers by surface chemistry engineering. They can be used as transfection agents for cardiomyocytes and we have shown that TiONts can increase the ionizing effect of radiation therapy in the case of glioblastoma. Furthermore, TiONts' biodistribution has been evaluated by SPECT/CT in male Swiss nude mice and TiONts are quickly cleared. More recently, we have demonstrated that TiONts-docetaxel (DTX) nanohybrids are versatile nanocarriers to limit the systemic toxicity of taxanes and to improve the selectivity of radiotherapy (RT). Our strategy is based on the intraprostatic injection of the TiONts-DTX nanohybrids both in place of brachytherapy and in combination with RT. This is achieved by taking advantage of the TiONts' morphology as well as their radiosensitization effect and by associating them with docetaxel molecules, also recognized for their radiosensitizing potential. We also grafted the surface of TiONts with gold nanoparticles, for a resulting combined radiosensitizing effect. The elaboration of nanohybrid materials, intended for drug delivery systems and based on TiONts coated with chitosan polymer has also been evaluated. Such nanotubes are combined with transresveratrol derivatives for their anti-oxidizing and antitumor effects. All the aspects of a potential toxicity are also considered.