Abstract
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Objectives Multifunctional theranostic agents have become rather attractive to realize image-guided combination cancer therapy. Herein, we develop a novel method to synthesize Bi2Se3 nanosheets decorated with mono-dispersed FeSe2 nanoparticles (FeSe2/Bi2Se3) for tetra-modal image-guided combined photothermal & radiation tumor therapy.
Methods Bi2Se3 nanosheets decorated with FeSe2 nanoparticles (FeSe2/Bi2Se3) were synthesized in a mixed solvent of oleylamine (OM) and 1-octadecene (ODE) under N2 atmosphere via a one-step cation exchange method. After that, PEG-grafted amphiphilic polymer was used to functionalize as-made FeSe2/Bi2Se3. Taking advantages of (i) high r2 relaxation of FeSe2, (ii) X-ray attenuation ability of Bi2Se3, (iii) strong near-infrared (NIR) absorbance of the whole nanostructure, and (iv) chelator-free radiolabeling ability of 64Cu on FeSe2/Bi2Se3-PEG, in vivo magnetic resonance (MR)/computer tomography (CT)/photoacoustic (PA)/position emission tomography (PET) multimodal imaging were investigated after intravenous injection. Utilizing the intrinsic physical properties of FeSe2/Bi2Se3-PEG, in vivo photothermal & radiation therapy were then carried out to achieve synergistic tumor destruction. At last, we also conducted a series of experiment including the biodistribution and blood biochemistry analysis to investigate the toxicity and clearance of these new materials
Results We developed a novel method to synthesize Bi2Se3 nanosheets decorated with mono-dispersed FeSe2 nanoparticles (FeSe2/Bi2Se3) for tetra-modal image-guided combined photothermal & radiation tumor therapy. Interestingly, upon addition of Bi(NO3)3, pre-made FeSe2 nanoparticles were gradually converted into Bi2Se3 nanosheets via cation exchange, and the remaining FeSe2 nanoparticles were decorated. After PEGylation, the FeSe2/Bi2Se3-PEG exhibited great stability in various physiological solutions. With a high r2 relaxivity, strong X-ray and NIR absorbance, as well as the chelate-free 64Cu radiolabeling, such nsnocomposite offered contrasts in tetra-modal MR/CT/PA/PET imaging, which vividly illustrates efficient tumor homing of FeSe2/Bi2Se3-PEG after i.v. injection. Again, utilizing the intrinsic physical properties of FeSe2/Bi2Se3-PEG, in vivo photothermal & radiation therapy (PTT&RT) with a remarkable synergistic tumor destruction effect were achieved. Upon systemic administration, FeSe2/Bi2Se3-PEG showed relatively rapid excretion with little retention.
Conclusions FeSe2/Bi2Se3 nanostructures were successfully synthesized via cation exchange and successfully used for multimodal imaging and synergistic tumor therapy. By carefully changing the amount of added Bi, the density of FeSe2 nanoparticles decorated on the surface of the Bi2Se3 nanosheets could be tuned. Utilizing the intrinsic physical properties of FeSe2/Bi2Se3-PEG, in vivo tetra-modal MR/CT/PA/PET imaging and combined PTT&RT therapy were successfully accomplished. Our work presented a unique method to synthesize composite-nanostructures with highly integrated functionalities that is useful for nano-biomedicine and also potentially useful for other different nanotechnology fields. $$graphic_2160DFFD-7263-4B79-BC62-F431E4981309$$