Evaluation of a PSMA-targeted BNF nanoparticle construct.
Evaluation of a PSMA-targeted BNF nanoparticle construct.
复制标题
评估靶向PSMA的BNF纳米颗粒构建体。
DOI：
10.1039/c4nr06069e
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发表时间：
2015-03-14
期刊：
影响因子：
6.7
通讯作者：
Pomper MG
中科院分区：
文献类型：
--
作者：
Behnam Azad B;Banerjee SR;Pullambhatla M;Lacerda S;Foss CA;Wang Y;Ivkov R;Pomper MG
早期发现可以改善前列腺癌(PCA)的预后。前列腺癌成像和治疗的一个有希望的靶点是前列腺特异性膜抗原(PSMA)，它在前列腺癌细胞的上皮细胞中都有表达，并在与配体结合后内化。在这里，我们报道了一种以PSMA为靶点的生物化纳米铁氧体(BNF)纳米颗粒的合成，并在PCA的实验模型中进行了生物学评价。BNF纳米颗粒配方显示出有利于靶向成像的特性，如隐形、延长循环时间和增强对非靶点的清除。体内靶向BNF的光学成像显示，PSMA+肿瘤在注射后4小时优先积聚，提示靶向特异性。另一方面，非靶向纳米粒在PSMA+和PsM−肿瘤中的摄取较低，积聚相似，表明肿瘤的进入没有优先积聚。单光子发射计算机断层扫描和生物分布研究表明，肿瘤在注射后48h达到最大聚集量[(4.3±0.4)%组织注射剂量(%ID g−1)]，肿瘤/血液和肿瘤/肌肉比值分别为7.5±2.4和11.6±1.2%ID g−1。体外荧光显微镜、普鲁士蓝染色、免疫组织化学和生物分布研究证实，与不表达PSMA的肿瘤相比，PSMA+的肿瘤对纳米颗粒的摄取增强。所描述的BNF纳米制剂有望在体内应用于PSMA靶向成像。
Early detection enables improved prognosis for prostate cancer (PCa). A promising target for imaging and therapy of PCa is the prostate-specific membrane antigen (PSMA), which exhibits both expression within the epithelium of PCa cells, and becomes internalized upon ligand binding. Here we report the synthesis of a PSMA-targeted bionized nanoferrite (BNF) nanoparticle and its biological evaluation in an experimental model of PCa. The BNF nanoparticle formulation exhibits properties conducive to targeted imaging such as stealth, prolonged circulation time and enhanced clearance from non-target sites. Optical imaging of the targeted BNF in vivo indicates preferential accumulation in PSMA+ tumors 4 h post-injection, suggesting target specificity. On the other hand, non-targeted nanoparticles exhibit lower uptake with similar accumulation in both PSMA+ and PSM− tumors indicating tumor access without preferential accumulation. Imaging with single photon emission computed tomography (SPECT) and biodistribution studies of a modified construct indicate highest tumor accumulation at 48 h post-injection [4.3 ± 0.4 percentage injected dose per gram of tissue (%ID g−1)], with tumor/blood and tumor/muscle ratios of 7.5 ± 2.4 and 11.6 ± 1.2 %ID g−1, respectively. Ex vivo fluorescence microscopy, Prussian blue staining, immunohistochemistry and biodistribution studies confirm enhanced nanoparticle uptake in PSMA+ tumors compared to those not expressing PSMA. The BNF nano-formulation described is promising for PSMA-targeted imaging applications in vivo.
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DOI：
10.1016/j.jconrel.2013.08.300
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Kullberg M;McCarthy R;Anchordoquy TJ
通讯作者：
Anchordoquy TJ
影响因子：
3.5
作者：
Dennis CL;Jackson AJ;Borchers JA;Hoopes PJ;Strawbridge R;Foreman AR;van Lierop J;Grüttner C;Ivkov R
通讯作者：
Ivkov R
面对药物输送中纳米技术的真相。
影响因子：
17.1
作者：
Park K
通讯作者：
Park K
影响因子：
78.8
作者：
Jain, Rakesh K.;Stylianopoulos, Triantafyllos
通讯作者：
Stylianopoulos, Triantafyllos
影响因子：
6.4
作者：
Mhawech-Fauceglia, P.;Zhang, S.;Penetrante, R.
通讯作者：
Penetrante, R.