Optical and MRI-Guided Theranostic Application of Ultrasmall Superparamagnetic Iron Oxide Nanodrug Conjugate for PSMA-Positive Prostate Cancer Therapy

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Optical and MRI-Guided Theranostic Application of Ultrasmall Superparamagnetic Iron Oxide Nanodrug Conjugate for PSMA-Positive Prostate Cancer Therapy

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Optical and MRI-Guided Theranostic Application of Ultrasmall Superparamagnetic Iron Oxide Nanodrug Conjugate for PSMA-Positive Prostate Cancer Therapy

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

21001 - Nano-materials (production and properties)

Projekt

<a href="/cs/project/LUAUS23254" target="_blank" >LUAUS23254: Proteinové inženýrství v přípravě humanizovaných protilátek pro zobrazování pro léčbu nádorů prostaty</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Applied Materials and Interfaces

ISSN

1944-8244

e-ISSN

1944-8252

Svazek periodika

17

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

11611-11623

Kód UT WoS článku

001419469700001

EID výsledku v databázi Scopus

2-s2.0-85218479314