Radiolabeled Human Protein-Functionalized Upconversion Nanoparticles for Multimodal Cancer Imaging

Najim Akhtar, Pei Wen Wu, Chuan Lin Chen, Wen Yi Chang, Ren-Shyan Liu, Chien Ting Wu, Agnishwar Girigoswami, Surojit Chattopadhyay*

*此作品的通信作者

研究成果: Article同行評審

摘要

Multimodal imaging removes the intrinsic limitations of individual modalities, while the multipurpose nanoagents reduce the toxicity associated with the use of multiple contrast agents. However, limited functionality, inefficient or incompatible targeting, and unknown biodistribution are significant drawbacks for such complicated nanodesigns. We report a biofriendly pentamodal imaging agent with the synergistic dual-targeting ability (passive and active) based on fluoromagnetic NaGdF4:Yb,Er upconverting nanoparticles (UCNPs). Besides the nano-enabled passive targeting, the apo-human serum transferrin protein (Tf) conjugation actively targets the transferrin receptors (TfR) over-expressed on different cancer cells. The radiolabel, 99mTc, chelates in the Tf core increase the radiolabeling efficiency (∼95%) and stability (∼100% for 24 h), enabling efficient single-photon emission computed tomography imaging. Deep-penetrating 980 nm excited UCNPs are inherently active luminescent and photothermal agents enabling fluorescence and photothermal imaging, respectively. The Gd in UCNPs produces a T1-weighted MRI signal, and the Yb helps in computed tomography (CT) as contrast agents. A pentamodal imaging agent (UCNP@Tf-99mTc) with synergistic dual-targeting ability is thus designed. In vitro studies demonstrated receptor-mediated endocytosis and minimal cytotoxicity of the UCNP@Tf-99mTc nanoformulation (>75% cell viability at 1000 ppm). The in vivo biodistribution studies in the mice model under SPECT/CT revealed its near-ideal bioavailability and renal clearance behavior. The MRI investigation on 4 T1 tumor-bearing mice brought direct evidence of passive and synergistic passive-active targeted tumor accumulation of the nanoformulation. The in vivo multimodal tumor imaging (MRI/SPECT/thermal-camera/CT) demonstrates the potency of UCNP@Tf-99mTc as a single replacement for multiple imaging agents and a perfect candidate for the ultramodern Advanced Multimodality Image Guided Operating (AMIGO) suite.

原文English
頁(從 - 到)7051-7062
頁數12
期刊ACS Applied Nano Materials
5
發行號5
DOIs
出版狀態Published - 27 5月 2022

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