Journal
NANO LETTERS
Volume 21, Issue 11, Pages 4692-4699Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c00895
Keywords
Silica nanoparticles; Theranostics; Nanotheranostics; PET imaging; Yttrium-90; Yttrium-86
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Funding
- University of Wisconsin - Madison
- National Institutes of Health [P30CA014520]
- Brazilian Science Without Borders Program (SwB-CNPq)
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Theranostic nanoparticles, specifically ultrasmall porous silica nanoparticles (UPSN) conjugated with isotopic pair Y-90/86, show promising in vivo pharmacokinetics with high target tissue accumulation and evasion from RES organs. These UPSN demonstrate both noninvasive imaging and internal radiotherapy capabilities, holding potential for future clinical translation as cancer theranostic agents.
Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair Y-90/86, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with Y-86-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 +/- 1.7 and 1.5 +/- 0.5, respectively), unprecedented for inorganic nanomaterials. Y-90-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.
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