DEVELOPMENT OF A COMPOSITE OF POLYPYRROLE-COATED CARBON NANOTUBES AS A SONOSENSITIZER FOR TREATMENT OF MELANOMA CANCER UNDER MULTI-STEP ULTRASOUND IRRADIATION
ULTRASOUND IN MEDICINE AND BIOLOGY
Authors: Behzadpour, Niloufar; Ranjbar, Aliyeh; Azarpira, Negar; Sattarahmady, Naghmeh
Abstract
Sonodynamic therapy (SDT) has established a novel route for treating solid cancers. Low-intensity ultrasound irradiation accompanied by a sonosensitizer has revealed remarkable advantages for cancer therapy such as targeted uptake, access to deeper tumors, insignificant side effects and invasiveness, compared with other therapeutic methods. In this study, we scrutinized synthesis and characterization of a polypyrrole-coated multi-walled carbon nanotubes composite (PPy@MWCNTs). PPy@MWCNTs can absorb ultrasound irradiation by both of its components, and it was introduced as a new sonosensitizer. The composite was characterized by field emission scanning electron microscopy (FESEM), and its ability to temperature elevation was explored. FESEM images revealed that PPy@MWCNTs comprised nanotubes of 36.3 +/- 5.1 nm in diameter with up to several micrometer in length. Ultrasound irradiation at 1 MHz and 1.0 W cm(-2) for 60 s in four steps led to an efficient SDT in vitro (16.3 +/- 2.8 degrees C temperature increment for 250 mu g mL(-1) of PPy@MWCNTs), in C540 (B16/F10) cell line and a melanoma tumor model in male balb/c mice. In vitro examinations revealed that PPy@MWCNTs represented a concentration-dependent cytotoxicity on multi-step ultrasound irradiation (a cell viability of 8.9% for 250 mu g mL(-1) of PPy@MWCNTs). Histologic analyses and tumor volume decrement after 10 d revealed detrimental SDT effects of PPy@MWCNTs on tumors (75% necrosis and 50% decrement in tumor volume). Thermal effects and reactive oxygen species generation were the reasons of the working function of PPy@MWCNTs in SDT. (C) 2020 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
Synthesis and Relaxometric Characterization of New Poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) Dendrons Gd-Based Contrast Agents and Their in Vivo Study by Using the Dynamic Contrast-Enhanced MRI Technique at Low Field (1 T)
CHEMISTRY & BIODIVERSITY
Authors: Granato, Luigi; Longo, Dario; Boutry, Sebastien; Vander Elst, Luce; Henoumont, Celine; Aime, Silvio; Muller, Robert N.; Laurent, Sophie
Abstract
The synthesis of poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) dendrons Gd-based contrast agents (GdCAs) via an orthogonal protection of the different functional groups and an activation/coupling strategy wherein a specific number of synthetic steps add a generation to the existing dendron has been described. The aim of this protocol is to build up two different generations of dendrons (G-0 or dendron's core, and G-1) with peripheral NH2 groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd3+ paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher H-1 relaxivity by slowing down the rotation of molecule compared to monomeric Gd(III) complexes used as contrast agents and to increase the number of paramagnetic centers present in one molecular structure. From the study of their water H-1 longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature O-17-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting H-1 relaxivity. Furthermore, these two novel PAPGly GdCAs were objects of i) an in vivo study to determine their biodistributions in healthy C57 mice at several time points, and ii) the Dynamic Contrast-Enhanced MRI (DCE-MRI) approach to assess their contrast efficiency measured in the tumor region of C57BL/6 mice transplanted subcutaneously with B16-F10 melanoma cells. The aim of the comparison of these two dendrons GdCAs, having different molecular weights (MW), is to understand how MW and relaxivity may influence the contrast enhancement capabilities in vivo at low magnetic field (1 T). Significant contrast enhancement was observed in several organs (vessel, spleen and liver), already at 5 min post-injection, for the investigated CAs. Moreover, these CAs induced a marked contrast enhancement in the tumor region, thanks to the enhanced permeability retention effect of those macromolecular structures.