Abstract
Radiolabeled nanoparticles (NPs), taking advantage of nanotechnology and nuclear medicine, have shown attractive potential for cancer diagnosis and therapy. However, the high background signal in the liver and long-term toxic effects of radioisotopes caused by the nonselective accumulation of radiolabeled nanoparticles in organs have become the major challenges. Here, we report a pH-sensitive multifunctional theranostic platform with radiolabeled Pd nanosheets through a simple mixture of ultra-small Pd nanosheets and radioisotopes utilizing the strong adsorption of 131I and 125I on their surfaces (denoted as 131I-Pd-PEG or 125I-Pd-PEG). Systematic studies reveal that the labeling efficiency is higher than 98% and the adsorption of radioiodine is more stable in an acidic environment. In vivo studies further validate the pH-dependent behavior of this platform and the enhanced retention of radioisotopes in tumors due to the acidic microenvironment. Single photon emission computed tomography (SPECT) images with zero background were successfully achieved in a subcutaneous 4T1 tumor model, an orthotopic LM3 tumor model, and even in a Mst1/2 double-knockout hepatoma model. Moreover, the application of radiolabeled Pd nanosheets for photoacoustic (PA) imaging, and combined photothermal and radiotherapy was also explored. Therefore, this study provides a simple and efficient strategy to solve the critical high background issue of radiolabeled nanoparticles and shows enormous potential for clinical applications.
Highlights
Radiolabeled nanoparticles (NPs) for positron emission tomography (PET) and single photon emission computed tomography (SPECT) have received special attention owing to their high sensitivity, deep tissue penetration and improved pharmacokinetics.[1]
131I labeled Pd–PEG (131I–Pd–PEG) showed a relatively high labeling efficiency
With the excellent labeling efficiency achieved under mild conditions, the simple radiolabeling processes reported in this work show great clinical translation potential
Summary
Radiolabeled nanoparticles (NPs) for positron emission tomography (PET) and single photon emission computed tomography (SPECT) have received special attention owing to their high sensitivity, deep tissue penetration and improved pharmacokinetics.[1]. The background signal caused by high accumulation of NPs in the liver has been the most crucial factor degrading the quality of imaging, even for those modi ed with active target molecules.1f,5 the long-term retention of radioisotopes in normal tissues may cause toxic effects in vivo. Most studies are focused on the imaging of subcutaneous xenogra tumors, and few reports have demonstrated their potential application in deep tissue imaging especially in orthotopic liver cancer. The development of radiolabeled NPs to minimize the background signal and maximize the tumor-tonormal tissue (T/N) ratio is highly desired
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