Docetaxel-titanate nanotubes enhance radiosensitivity in an androgen-independent prostate cancer model

Figures & data

Figure 1 TiONts-DTX and TiONts-DTX-DOTA[¹¹¹In] synthesis steps.

Notes: APTES-modified titanate nanotubes (TiONts-APTES) (A) are combined with α-acid-ω-thiol-poly(ethylene glycol) (HOOC-PEG-SH, MW =3,000 Da) (B) to generate PEGylated nanotubes (TiONts-PEG-SH) (C) by amide formation. In the second step, (C) is combined with PMPI-modified docetaxel (DTX-PMPI) (D) to finally yield the TiONts-PEG-DTX nanohybrid (E). The nanohybrid (E) is subjected to the reaction of amide formation in the presence of (iii) DOTA-NHS macrocycles to yield nanohybrid (F) (TiONts-DTX-DOTA). In a subsequent step, (F) allows the chelation of indium radionuclides (from ¹¹¹InCl₃) into DOTA macrocycles to produce SPECT-capable nanohybrid (G) (TiONts-DTX-DOTA[¹¹¹In]).

Abbreviations: APTES, 3-aminopropyl triethoxysilane; DTX, docetaxel; SPECT, single-photon emission computed tomography; TiONts, titanate nanotubes; PMPI, p-maleimidophenyl isocyanate.

Figure 2 TiONts-DTX cytotoxic activity evaluation.

Notes: PC-3 cells were treated with free DTX, activated DTX (DTX-PMPI), DTX grafted to TiONts (TiONts-DTX) or bare TiONts (concentration equivalent to TiONts-DTX) for 96 h. Each point corresponds to the mean values of five replicates ± SD (results shown are representative curves from two independent experiments).

Abbreviations: DTX, docetaxel; TiONts, titanate nanotubes; PMPI, p-maleimi-dophenyl isocyanate.

Figure 3 TiONts-DTX biodistribution analysis.

Notes: (A) SPECT-CT imaging of kinetics and biodistribution analysis for each organ (expressed as a percentage of injected ¹¹¹In activity, taking into account the decrease in ¹¹¹In activity after the injection of DOTA[¹¹¹In] (A1) or TiONts-DTX-DOTA[¹¹¹In] (A2)). (B) TiONts-DTX-DOTA[¹¹¹In] biodistribution in dissected organs by radioactivity detection using gamma counting 7 days after injection (mean value ± SD). (C) TEM images showing the intracellular location of TiONts-DTX 24 h after injection into PC-3 tumors.

Abbreviations: DTX, docetaxel; SPECT-CT, single-photon emission computed tomography-computed tomography; TEM, transmission electron microscopy; TiONts, titanate nanotubes.

Figure 4 Therapeutic effect of vehicle, free DTX, free TiONts, and TiONts-DTX associated or not with RT administered with three daily fractions of 4 Gy, 24 h after injection into PC-3 xenografted tumors.

Notes: Data are mean values of tumor volumes ± SD (n=7 per treatment group, eight treatment groups). *P=0.013 (TiONts-DTX + RT vs DTX + RT or TiONts + RT), comparison performed using nonparametric Mann–Whitney test.

Abbreviations: DTX, docetaxel; RT, radiotherapy; TiONts, titanate nanotubes.