Target-or-clear zirconium-89 labeled silica nanoparticles for enhanced cancer-directed uptake in melanoma: A comparison of radiolabeling strategies Journal Article
| Authors: | Chen, F.; Ma, K.; Zhang, L.; Madajewski, B.; Zanzonico, P.; Sequeira, S.; Gonen, M.; Wiesner, U.; Bradbury, M. S. |
| Article Title: | Target-or-clear zirconium-89 labeled silica nanoparticles for enhanced cancer-directed uptake in melanoma: A comparison of radiolabeling strategies |
| Abstract: | Designing a nanomaterials platform with high target-to-background ratios has long been one of the major challenges in the field of nanomedicine. Here, we introduce a "target-or-clear" multifunctional nanoparticle platform that demonstrates high tumor-targeting efficiency and retention while minimizing off-target effects. Encouraged by the favorable preclinical and clinical pharmacokinetic profiles derived after fine-tuning surface chemical properties of radioiodinated (124I, t1/2 = 100.2 h) ultrasmall cRGDY-conjugated fluorescent silica nanoparticles (C dots), we sought to investigate how the biological properties of these radioconjugates could be influenced by the conjugation of radiometals such as zirconium-89 (89Zr, t1/2 = 78.4 h) using two different strategies: chelator-free and chelator-based radiolabeling. The attachment of 89Zr to newer, surface-aminated, integrin-targeting C′ dots using a two-pot synthesis approach led to favorable pharmacokinetics and clearance profiles as well as high tumor uptake and target-to-background ratios in human melanoma models relative to biological controls while maintaining particle sizes below the effective renal glomerular filtration size cutoff <10 nm. Nanoconjugates were also characterized in terms of their radiostability and plasma residence half-lives. Our 89Zr-labeled ultrasmall hybrid organic-inorganic particle is a clinically promising positron emission tomography tracer offering radiobiological properties suitable for enhanced molecularly targeted cancer imaging applications. © 2017 American Chemical Society. |
| Keywords: | positron emission tomography; oncology; medical imaging; tumors; medical nanotechnology; nanoparticles; silica; fluorescent silica nanoparticles; dermatology; diseases; chelation; pharmacokinetics; clinical pharmacokinetics; biological properties; silica nanoparticles; glomerular filtration; hybrid organic-inorganic; multi-functional nanoparticles; surface chemical properties |
| Journal Title: | Chemistry of Materials |
| Volume: | 29 |
| Issue: | 19 |
| ISSN: | 0897-4756 |
| Publisher: | American Chemical Society |
| Date Published: | 2017-10-10 |
| Start Page: | 8269 |
| End Page: | 8281 |
| Language: | English |
| DOI: | 10.1021/acs.chemmater.7b02567 |
| PROVIDER: | scopus |
| PMCID: | PMC5675572 |
| PUBMED: | 29123332 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2017 -- Source: Scopus |
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