PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer.

PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer.
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DOI:
10.1016/j.colsurfb.2016.03.071
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发表时间:
2016-08-01
影响因子:
5.8
通讯作者:
Yallapu, Murali M.
Yallapu, Murali M.
中科院分区:
工程技术2区
文献类型:
--
作者:
Nagesh, Prashanth K. B.;Johnson, Nia R.;Boya, Vijaya K. N.;Chowdhury, Pallabita;Othman, Shadi F.;Khalilzad-Sharghi, Vahid;Hafeez, Bilal B.;Ganju, Aditya;Khan, Sheema;Behrman, Stephen W.;Zafar, Nadeem;Chauhan, Subhash C.;Jaggi, Meena;Yallapu, Murali M.

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多西他赛(Dtxl)是目前前列腺癌(PC)最常见的治疗选择。然而,与化疗耐药性相关的不良副作用和问题限制了其在临床环境中的治疗结果。靶向纳米颗粒系统,以改善其交付和在肿瘤部位的活性可能是一个有吸引力的策略PC治疗。因此,本研究的目的是开发和确定用于PC治疗的新型多西他赛负载的前列腺特异性膜抗原(PSMA)靶向超顺磁性氧化铁纳米颗粒(SPION)(J591-SPION-Dtxl)制剂的抗癌功效。我们的结果表明SPION-Dtxl制剂具有最佳的粒径和zeta电位,可以有效地内化在PC细胞中。SPION-Dtxl通过诱导PC细胞系中凋亡相关蛋白的表达、下调抗凋亡蛋白和抑制化疗耐药相关蛋白而表现出有效的抗癌功效。与PC-3(PSMA−)细胞相比,J591-SPION-Dtxl在C4-2(PSMA+)细胞中表现出显著摄取。在C4-2肿瘤的离体研究中观察到类似的靶向潜力,但在PC-3肿瘤中未观察到,表明其肿瘤特异性靶向。总之,本研究表明,PSMA抗体功能化SPION-Dtxl制剂可高度用于靶向PC治疗。
Docetaxel (Dtxl) is currently the most common therapeutic option for prostate cancer (PC). However, adverse side effects and problems associated with chemo-resistance limit its therapeutic outcome in clinical settings. A targeted nanoparticle system to improve its delivery to and activity at the tumor site could be an attractive strategy for PC therapy. Therefore, the objective of this study was to develop and determine the anti-cancer efficacy of a novel docetaxel loaded, prostate specific membrane antigen (PSMA) targeted superparamagnetic iron oxide nanoparticle (SPION) (J591-SPION-Dtxl) formulation for PC therapy. Our results showed the SPION-Dtxl formulation exhibits an optimal particle size and zeta potential, which can efficiently be internalized in PC cells. SPION-Dtxl exhibited potent anti-cancer efficacy via induction of the expression of apoptosis associated proteins, downregulation of anti-apoptotic proteins, and inhibition of chemo-resistance associated protein in PC cell lines. J591-SPION-Dtxl exhibited a profound uptake in C4-2 (PSMA+) cells compared to PC-3 (PSMA−) cells. A similar targeting potential was observed in ex-vivo studies in C4-2 tumors but not in PC-3 tumors, suggesting its tumor specific targeting. Overall this study suggests that a PSMA antibody functionalized SPION-Dtxl formulation can be highly useful for targeted PC therapy.
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