On-demand release of encapsulated ZnO nanoparticles and chemotherapeutics for drug delivery applications†

Josh E. Eixenberger, Catherine B. Anders, Rebecca Hermann, Katelyn Wada, Kongara M. Reddy, Raquel J. Montenegro-Brown, Daniel Fologea and Denise G. Wingett
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Abstract

Nanomedicines offer high promise for the treatment of various diseases, and numerous novel approaches using nanomaterials have been developed over the years. In this report, we introduce a new strategy utilizing ZnO nanoparticles (nZnO) to trigger the rapid release of lipid-encapsulated therapeutics upon photo-irradiation with UV light (365 nm). In vitro studies demonstrate that encapsulation of nZnO effectively eliminates the cytotoxicity of nZnO, but this can be re-established upon release from the lipid coating. Using 5(6)-carboxyfluorescein as a model for hydrophilic drug loading, we show the ability to co-load drugs with nZnO into liposomes. Kinetic studies reveal the ability to release the majority of the dye within 60 minutes post-photo-irradiation and provide insights into factors that impact release kinetics. To further explore this, Jurkat T cell leukemia and T47D breast cancer cells were treated with co-encapsulated nZnO and the hydrophobic cancer drug paclitaxel. These studies revealed enhanced toxicity of the triggered release groups with an extreme difference noted in the viability profiles of the T47D breast cancer cell model. Taken together, these studies indicate that this system of co-encapsulating nZnO and chemotherapeutic drugs has the potential to minimize systemic toxicity, by controlling therapeutic release, while allowing for the localized selective destruction of cancer.

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按需释放封装ZnO纳米颗粒和化疗药物递送应用。
纳米药物为治疗各种疾病提供了很大的希望,近年来已经开发了许多使用纳米材料的新方法。在本报告中,我们介绍了一种利用氧化锌纳米粒子(nZnO)在365 nm紫外光照射下触发脂质包封治疗药物快速释放的新策略。体外研究表明,nZnO包封有效地消除了nZnO的细胞毒性,但这可以在脂质包被释放后重新建立。使用5(6)-羧基荧光素作为亲水性药物装载模型,我们展示了与nZnO共同装载药物到脂质体中的能力。动力学研究揭示了光照射后60分钟内释放大部分染料的能力,并提供了影响释放动力学的因素的见解。为了进一步探讨这一点,我们用共包封的nZnO和疏水抗癌药物紫杉醇治疗Jurkat T细胞白血病和T47D乳腺癌细胞。这些研究表明,触发释放组的毒性增强,在T47D乳腺癌细胞模型的生存能力方面存在极大差异。综上所述,这些研究表明,这种共包埋nZnO和化疗药物的系统有可能通过控制治疗释放来最大限度地减少全身毒性,同时允许局部选择性破坏癌症。
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