Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner.
Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner.
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DOI：
10.2147/ijn.s34381
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发表时间：
2012
影响因子：
8
通讯作者：
Sillerud LO
中科院分区：
文献类型：
--
作者：
Taylor RM;Sillerud LO
前列腺癌临床管理的问题包括缺乏特异性检测和有效的治疗干预。我们报告了将超顺磁性铁铂纳米颗粒（SIPPs）和紫杉醇封装在聚乙二醇化、荧光和生物素功能化磷脂的混合物中，以产生多功能SIPP-PTX胶束（SPM），该胶束与抗前列腺特异性膜抗原（PSMA）的抗体缀合，用于特异性靶向、磁共振成像（MRI）和治疗小鼠中的人前列腺癌异种移植物。SPM直径为45.4 ± 24.9 nm，由160.7 ± 22.9 μg/mL铁、247.0 ± 33.4 μg/mL铂和702.6 ± 206.0 μg/mL紫杉醇组成。药物释放测量显示，在37°C下，一半的紫杉醇在血清中在30.2小时内释放，在盐水中快两倍。结合实验表明，靶向PSMA的SPM在体外特异性结合C4-2人前列腺癌细胞，并将紫杉醇释放到细胞中。在体外，紫杉醇的2.2和1.6倍以上的细胞毒性比SPM的C4-2细胞在24和48小时的孵育，分别。孵育72小时后，紫杉醇和SPM具有相同的细胞毒性。SPM具有389 ± 15.5 Hz/mM铁的MRI横向弛豫率，并且具有和不具有药物的SIPP胶束在体内引起MRI对比度增强。只有靶向PSMA的SPM和紫杉醇显著阻止裸鼠中C4-2前列腺癌异种移植物的生长。此外，与非靶向SPM注射和紫杉醇注射小鼠相比，注射PSMA靶向SPM的小鼠在肿瘤中显示出显著更多的紫杉醇和铂。
Problems with the clinical management of prostate cancer include the lack of both specific detection and efficient therapeutic intervention. We report the encapsulation of superparamagnetic iron platinum nanoparticles (SIPPs) and paclitaxel in a mixture of polyethyleneglycolated, fluorescent, and biotin-functionalized phospholipids to create multifunctional SIPP-PTX micelles (SPMs) that were conjugated to an antibody against prostate-specific membrane antigen (PSMA) for the specific targeting, magnetic resonance imaging (MRI), and treatment of human prostate cancer xenografts in mice. SPMs were 45.4 ± 24.9 nm in diameter and composed of 160.7 ± 22.9 μg/mL iron, 247.0 ± 33.4 μg/mL platinum, and 702.6 ± 206.0 μg/mL paclitaxel. Drug release measurements showed that, at 37°C, half of the paclitaxel was released in 30.2 hours in serum and two times faster in saline. Binding assays suggested that PSMA-targeted SPMs specifically bound to C4-2 human prostate cancer cells in vitro and released paclitaxel into the cells. In vitro, paclitaxel was 2.2 and 1.6 times more cytotoxic than SPMs to C4-2 cells at 24 and 48 hours of incubation, respectively. After 72 hours of incubation, paclitaxel and SPMs were equally cytotoxic. SPMs had MRI transverse relaxivities of 389 ± 15.5 Hz/mM iron, and SIPP micelles with and without drug caused MRI contrast enhancement in vivo. Only PSMA-targeted SPMs and paclitaxel significantly prevented growth of C4-2 prostate cancer xenografts in nude mice. Furthermore, mice injected with PSMA-targeted SPMs showed significantly more paclitaxel and platinum in tumors, compared with nontargeted SPM-injected and paclitaxel-injected mice.