Bakewell Suzanne J, Carie Adam, Costich Tara L, Sethuraman Jyothi, Semple J Edward, Sullivan Bradford, Martinez Gary V, Dominguez-Viqueira William, Sill Kevin N
Intezyne Technologies, Tampa, FL, USA.
Intezyne Technologies, Tampa, FL, USA.
Nanomedicine. 2017 May;13(4):1353-1362. doi: 10.1016/j.nano.2017.01.009. Epub 2017 Jan 20.
Nanoparticle drug carriers hold potential to improve current cancer therapy by delivering payload to the tumor environment and decreasing toxic side effects. Challenges in nanotechnology drug delivery include plasma instability, site-specific delivery, and relevant biomarkers. We have developed a triblock polymer comprising a hydroxamic acid functionalized center block that chelates iron to form a stabilized micelle that physically entraps chemotherapeutic drugs in the hydrophobic core. The iron-imparted stability significantly improves the integrity of the micelle and extends circulation pharmacokinetics in plasma over that of free drug. Furthermore, the paramagnetic properties of the iron-crosslinking exhibits contrast in the tumors for imaging by magnetic resonance. Three separate nanoparticle formulations demonstrate improved anti-tumor efficacy in xenograft models and decreased toxicity. We report a stabilized polymer micelle that improves the tolerability and efficacy of chemotherapeutic drugs, and holds potential for non-invasive MRI to image drug delivery and deposition in the tumor.
纳米颗粒药物载体有望通过将有效载荷递送至肿瘤环境并减少毒副作用来改善当前的癌症治疗。纳米技术药物递送面临的挑战包括血浆不稳定性、靶向递送以及相关生物标志物。我们开发了一种三嵌段聚合物,其包含一个异羟肟酸功能化的中心嵌段,该嵌段螯合铁以形成稳定的胶束,从而将化疗药物物理包裹在疏水核心中。铁赋予的稳定性显著提高了胶束的完整性,并延长了其在血浆中的循环药代动力学,超过游离药物。此外,铁交联的顺磁性特性在肿瘤中产生对比,可用于磁共振成像。三种不同的纳米颗粒制剂在异种移植模型中显示出提高的抗肿瘤功效和降低的毒性。我们报道了一种稳定的聚合物胶束,它提高了化疗药物的耐受性和疗效,并具有通过非侵入性磁共振成像来观察药物在肿瘤中的递送和沉积的潜力。