The Russell H. Morgan Department of Radiology and Radiological Science , Johns Hopkins University School of Medicine , Baltimore , Maryland 21287 , United States.
The Sidney Kimmel Comprehensive Cancer Center , Johns Hopkins University School of Medicine , Baltimore , Maryland 21231 , United States.
Mol Pharm. 2019 May 6;16(5):2060-2068. doi: 10.1021/acs.molpharmaceut.9b00036. Epub 2019 Apr 10.
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-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.
磁性纳米颗粒（MNP）诱导的热疗目前正在用于局部前列腺癌的评估。我们通过静脉内给予 MNP（浓度足以进行热疗），在高分辨率磁共振成像（MRI）下评估了前列腺特异性膜抗原（PSMA）靶向 MNP 在具有高分辨率磁共振成像（MRI）的小鼠模型中的肿瘤选择性递送的可行性。合成了一种 PSMA 靶向 MNP，并在静脉内给予 50mg/kg 的 MNP 后使用 T 加权 MRI 进行了评估。与 PSMA（-）肿瘤相比，在造影剂给药后 24 小时和 48 小时，PSMA（+）肿瘤观察到明显的对比增强（P < 0.0002，n = 5）。还通过近红外荧光成像对小鼠进行了成像，以验证 MRI 结果。双光子显微镜显示肿瘤边缘的血管密度更高，导致 PSMA 靶向 MNP 的外周积累更高。这些结果表明，PSMA 靶向 MNP 递送到 PSMA（+）肿瘤是主动靶向和被动介导的。
