Optical and MRI-Guided Theranostic Application of Ultrasmall Superparamagnetic Iron Oxide Nanodrug Conjugate for PSMA-Positive Prostate Cancer Therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00647817" target="_blank" >RIV/86652036:_____/25:00647817 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsami.4c16009" target="_blank" >https://pubs.acs.org/doi/10.1021/acsami.4c16009</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsami.4c16009" target="_blank" >10.1021/acsami.4c16009</a>
Alternative languages
Result language
angličtina
Original language name
Optical and MRI-Guided Theranostic Application of Ultrasmall Superparamagnetic Iron Oxide Nanodrug Conjugate for PSMA-Positive Prostate Cancer Therapy
Original language description
Active targeting is more effective than conventional passive targeted drug delivery systems in increasing therapeutic efficacy and minimizing systemic toxicities. Importantly, the nanoparticle-based targeted drug delivery systems combine active and passive targeting properties and significantly enhance therapeutic efficacy. In this study, we utilized ultrasmall superparamagnetic iron oxide (uSPIO) nanoparticles conjugated with anti-prostate-specific membrane antigen (PSMA) 5D3 monoclonal antibody, mertansine (DM1) antitubulin agent, and fluorophore to develop a targeted uSPIO-5D3-DM1-AF488/CF750 nanotheranostic for PSMA(+) prostate cancer (PC) therapy. This agent enables multimodality in vivo imaging using near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI). uSPIO-5D3-DM1-AF488 is selectively internalized into PSMA-positive cells by receptor-mediated endocytosis, and uSPIO-5D3-DM1-CF750 exhibited 1.62 and 166.2 ng/mL IC50 values in PSMA(+) and PSMA(-) cells, respectively. The image-guided therapeutic study was conducted in vivo in human PC xenograft mouse models bearing bilateral PSMA(+/-) tumors (n = 10, two 10 mg/kg doses on days 1 and 14). The therapeutic results exhibited a significant control of the growth of PSMA(+) tumors starting at day 5 (p = 0.05) and significantly improved efficacy after day 9 (p = 0.0005) during the treatment period (t = 21 days). We observed the PSMA-specific uptake of uSPIO-5D3-DM1-CF750 in tumors in NIR IVIS Xenogen images and T 1- and T 2-weighted MRI with 20.6% and 42% reduction of overall T 1 and T 2, respectively. Approximately 70% of mice with PSMA(+) tumors treated with uSPIO-5D3-DM1-CF750 survived or did not exceed the threshold level of the tumor size during the treatment. Ex vivo biodistribution study proved 50% and 45% higher uptake of uSPIO-5D3-DM1-CF750 by PSMA(+) tumors compared to untargeted uSPIO-DM1-CF750 by PSMA(+) tumors and uSPIO-5D3-DM1-CF750 by PSMA(-) tumors, respectively. ICP-MS analysis demonstrated a 73% increase in uSPIO-5D3-DM1-CF750 uptake by PSMA(+) tumors compared to PSMA(+) tumors treated with pure uSPIO. The toxicological results reveal the safe profile in systemic toxicities without life-threatening changes in the complete blood count and clinical chemistry profile of toxicology.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
21001 - Nano-materials (production and properties)
Result continuities
Project
<a href="/en/project/LUAUS23254" target="_blank" >LUAUS23254: Design and characterization of humanized antibodies for prostate cancer imaging and therapy</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Applied Materials and Interfaces
ISSN
1944-8244
e-ISSN
1944-8252
Volume of the periodical
17
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
11611-11623
UT code for WoS article
001419469700001
EID of the result in the Scopus database
2-s2.0-85218479314