Titanate nanotubes as new preclinical theranostic platform against prostate cancer: vectorization and immobilization of docetaxel or of gold nanoparticles

Titanate nanotubes (TiONts) are synthetized by a hydrothermal process [1]. Their uncommon morphology obtained by controlled parameters allows them to be internalized more easily into cells. This permits their use as novel... [ view full abstract ]

Titanate nanotubes (TiONts) are synthetized by a hydrothermal process [1]. Their uncommon morphology obtained by controlled parameters allows them to be internalized more easily into cells. This permits their use as novel transfection agents [2] without inducing cytotoxicity while providing a radiosensitization effect [3]. These TiONts are combined to docetaxel (DTX), a molecule widely used for the treatment of cancers. Currently, injected drugs only reach very weakly tumor sites. In the last decade, the development of nanotechnologies has offered a new strategy to vectorize an active substance. In this work, two developments of nanohybrids are presented to fight against prostate cancer [4]: the first approach consists in combining TiONts and DTX and in a second one TiONts and gold nanoparticles (AuNPs) are combined together. This project is based on intraprostatic injection of the nanohybrids.

A particular attention was paid on the elaboration of functionalized-TiONts nanohybrids. On the one hand, docetaxel molecules were grafted by an original pathway onto TiONts. DOTA macrocycles were also grafted on the latter, allowing a radiotracer to be chelated, in order to evaluate the biodistribution of TiONts in mice by nuclear imaging. Biodistribution kinetics showed that more than 70% of nanohybrids were localized into the tumor 96 hours after injection. Mice receiving nanohybrid-RT (Radiation Therapy) exhibited a significant tumor growth delay compared to mice receiving free DXL-RT [5]. On the other hand, AuNPs functionalized by DTDTPA molecules are grafted on TiONts. This combination confers not only the nanovectorization via TiONts but also therapeutic effect via AuNPs [6]. In both cases, the suspension stability of nanohybrids was increased by the addition of biocompatible polyethylene oxide polymers and physico-chemical characterizations were realized to assert each functionalization step of our engineered nanohybrids.

References:
[1] A.-L. Papa et al., J. Phys. Chem. C, 113 (2009)
[2] A.-L. Papa et al., Nanotoxicology, 7, 6 (2013)
[3] C. Mirjolet et al., Radiother. Oncol., 108, 1 (2013)
[4] J. Boudon et al., Nanomedecine. O. C. Press: chapt 16
[5] C. Mirjolet et al., Eur. J. Cancer, 50, 6 (2014)
[6] C. Alric et al., Gold Bulletin, 41, 2 (2008)