Construction of tumor-cell nucleus targeting lanthanide nano-prodrugs with lutetium-177 labelling for high-efficient tumor fluorescence-localization and radionuclide therapy
Tumor-cell nucleus targeting is highly desired for theragnostic nano-prodrugs (NPDs) to enhance cancer diagnostic and therapeutic efficacy as compared to those targeting the cytoplasm or other intracellular organelles. This study presents a well-designed tumor-cell nucleus targeting theragnostic NPD...
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Published in | Nano today Vol. 55; p. 102214 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Ltd
01.04.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Tumor-cell nucleus targeting is highly desired for theragnostic nano-prodrugs (NPDs) to enhance cancer diagnostic and therapeutic efficacy as compared to those targeting the cytoplasm or other intracellular organelles. This study presents a well-designed tumor-cell nucleus targeting theragnostic NPD called 177Lu-YNP@FA that can not only deliver bright upconversion/NIR-II fluorescence but also emit radioactive β-ray radiation for efficient tumor fluorescence localization and radionuclide therapy, based on PEGylated folic acid (FA) decorated NaYF4:Yb/Er@NaYF4 core-shell nanocrystals with radionuclide lutetium-177 labeling. Owing to their unique tumor-cell nucleus targeting capacity, the well-designed 177Lu-YNP@FA NPDs can rapidly target the nuclei of Hela cells within eight hours, thereby allowing for the precise localization of two-hundred-micron-sized metastatic tumors of cervical carcinoma, even in the abdominal cavity of a living mouse model, through NIR-II fluorescence imaging. Importantly, these 177Lu-YNP@FA NPDs exhibit superior tumor accumulation (∼24.6%) and retention (∼7.1 days) compared to the NPDs without tumor-cell nucleus targeting ability. This results in highly efficient anticancer outcomes, both in vitro and in vivo, through a pyroptosis-mediated cell death associated with intracellular β-ray radiation of 177Lu radionuclide. These findings have significant implications for the intelligent design of organelle-specific targeting theranostic NPDs, offering new options for diagnosis and treatment in radiopharmaceutical therapy of cancer.
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•A new type of theragnostic nano-prodrug (NPD) with highly desirable tumor-cell nucleus targeting capability is proposed.•The resultant NPD can specially differentiate the tumor cells from the normal cells even within co-cultured conditions.•The resultant NPD is exploited for synergistic tumor-targeted bioimaging and imaging-guided surgery in vivo.•The resultant 177Lu-YNP@FA NPDs can be used as highly efficient radiopharmaceuticals for radiotherapy treatment of cervical carcinoma. |
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ISSN: | 1748-0132 1878-044X |
DOI: | 10.1016/j.nantod.2024.102214 |