Journal
MOLECULAR PHARMACEUTICS
Volume 16, Issue 5, Pages 2060-2068Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b00036
Keywords
prostate cancer; MNP; magnetic resonance imaging; optical imaging; magnetic hyperthermia therapy
Funding
- National Institutes of Health [R01CA134675, U01CA183031, P50CA058236, P41EB024495, K25CA148901]
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Magnetic nanoparticle (MNP)-induced hyperthermia is currently being evaluated for localized prostate cancer. We evaluated the feasibility of tumor-selective delivery of prostate-specific membrane antigen (PSMA)-targeted MNPs in a murine model with high-resolution magnetic resonance imaging (MRI) after intravenous administration of MNPs at a concentration necessary for hyperthermia. A PSMA-targeted MNP was synthesized and evaluated using T-2-weighted MRI, after intravenous administration of 50 mg/kg of the MNP. Significant contrast enhancement (P < 0.0002, n = 5) was observed in PSMA(+) tumors compared to PSMA(-) tumors 24 h and 48 h after contrast agent administration. Mice were also imaged with near-infrared fluorescence imaging, to validate the MRI results. Two-photon microscopy revealed higher vascular density at the tumor periphery, which resulted in higher peripheral accumulation of PSMA-targeted MNPs. These results suggest that the delivery of PSMA-targeted MNPs to PSMA(+) tumors is both actively targeted and passively mediated.
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