Laser-Ablative Synthesis of Stable Aqueous Solutions of Elemental Bismuth Nanoparticles for Multimodal Theranostic Applications.

Julia C Bulmahn,Andrei V Kabashin,Andrey Kuzmin,Paras N Prasad,Sergey M Klimentov,Gleb Tikhonowski,Anton A Popov

doi:10.3390/nano10081463

Abstract

Elemental bismuth (Bi) nanoparticles (NPs), with the high atomic density of the Bi nuclei, could serve as efficient targeted agents for cancer treatment, with applications such as contrast agents for computed tomography (CT) imaging, sensitizers for image-guided X-ray radiotherapy, and photothermal therapy. However, the synthesis of elemental Bi NPs suitable for biological applications is difficult using conventional chemical routes. Here, we explore the fabrication of ultrapure Bi-based nanomaterials by femtosecond laser ablation from a solid Bi target in ambient liquids and characterize them by a variety of techniques, including TEM, SEM, XRD, FTIR, Raman, and optical spectroscopy. We found that laser-ablative synthesis using an elemental Bi solid target leads to the formation of spherical Bi NPs having the mean size of 20–50 nm and a low size-dispersion. The NPs prepared in water experience a fast (within a few minutes) conversion into 400–500 nm flake-like nanosheets, composed of bismuth subcarbonates, (BiO)2CO3 and (BiO)4CO3(OH)2, while the NPs prepared in acetone demonstrate high elemental stability. We introduce a procedure to obtain a stable aqueous solution of elemental Bi NPs suitable for biological applications, based on the coating of Bi NPs prepared in acetone with Pluronic® F68 and their subsequent transfer to water. We also show that the laser-synthesized elemental Bi NPs, due to their vanishing band gap, exhibit remarkable absorption in the infrared range, which can be used for the activation of photothermal therapy in the near IR-to-IR window with maximum optical transparency in biological media. Exempt of any toxic synthetic by-products, laser-ablated elemental Bi NPs present a novel appealing nanoplatform for combination image-guided photoradiotherapies.

Highlights

Nanomaterials with high atomic numbers (Z) have demonstrated their ability to act as efficient sensitizers of radiotherapy (RT) [1,2,3]
When these high-Z elements are irradiated with X-rays, the result is a high local ionization effect leading to DNA strand breaks and enhancing the efficacy of RT
As a metal, elemental Bi strongly absorbs light over a broad spectral range extending to IR, which allows the resulting photothermal heating of elemental Bi nanoparticles by an IR light to be used for photoacoustic imaging as well as for photothermal therapy, which can synergistically enhance radiotherapy [3]

Summary

Introduction

Nanomaterials with high atomic numbers (Z) have demonstrated their ability to act as efficient sensitizers of radiotherapy (RT) [1,2,3]. Laser ablation in water has yielded only stable Bi compound NPs (oxides, carbonates, etc.), which cannot provide the maximum local concentration of Bi nuclei in comparison to elemental Bi, as a high concentration of Bi would reduce the needed dose level for radiotherapy and would enhance the contrast for imaging. We report the fabrication of stable aqueous solutions of ultrapure elemental Bi NPs by laser ablation in acetone, followed by their coating with Pluronic® F68 and transfer to water in unchanged form. This suggests that a proper surface modification of laser-synthesized Bi NPs is a plausible method to prepare stable, biocompatible, and pure Bi NPs for applications in nanomedicine

Synthesis of Nanoparticles

Photothermal Gradient Measurement

Conclusions