Magnetically Responsive Peptide Coacervates for Dual Hyperthermia and Chemotherapy Treatments of Liver Cancer

Z. Lim, V. Varma, R. Ramanujan, A. Miserez
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引用次数: 35

Abstract

Liver cancer is an aggressive malignancy associated with high levels of mortality and morbidity. Doxorubicin (Dox) is often used to slow down liver cancer progression; however its efficacy is limited, and its severe side effects prevent its routine use at therapeutic concentrations. We present a biomimetic peptide that coacervates into micro-droplets, within which both Dox and magnetic nanoparticles (MNPs) can be sequestered. These Dox-loaded Magnetic Coacervates (DMCs) can be used for thermo-chemotherapy, with the controlled release of Dox triggered by an external Alternating Magnetic Field (AMF). The DMCs are internalized by the cells via an energy-independent mechanism which is not based on endocytosis. Application of AMF generates a temperature of 45°C within the DMCs, triggering their disassembly and the simultaneous release of Dox, thereby resulting in dual hyperthermia and chemotherapy for more efficient cancer therapy. In vitro studies conducted under AMF reveal that DMCs are cytocompatible and effective in inducing HepG2 liver cancer cell death. Thermo-chemotherapy treatment against HepG2 cells is also shown to be more effective compared to either hyperthermia or chemotherapy treatments alone. Thus, our novel peptide DMCs can open avenues in theranostic strategies against liver cancer through programmable, wireless, and remote control of Dox release.
磁反应肽凝聚剂在肝癌热疗和化疗双重治疗中的应用
肝癌是一种具有高死亡率和高发病率的恶性肿瘤。阿霉素(Dox)常用于减缓肝癌的进展;然而,它的功效是有限的,其严重的副作用使其无法在治疗浓度下常规使用。我们提出了一种仿生肽,它凝聚成微滴,其中Dox和磁性纳米颗粒(MNPs)可以被隔离。这些负载Dox的磁性凝聚体(DMCs)可用于热化疗,由外部交变磁场(AMF)触发Dox的可控释放。dmc通过不依赖于内吞作用的能量独立机制被细胞内化。AMF在dmc内产生45°C的温度,触发其分解并同时释放Dox,从而产生双重热疗和化疗,以更有效地治疗癌症。在AMF下进行的体外研究表明,dmc具有细胞相容性,可有效诱导HepG2肝癌细胞死亡。针对HepG2细胞的热化疗也被证明比单独热疗或化疗更有效。因此,我们的新型肽dmc可以通过可编程、无线和远程控制Dox释放,为肝癌的治疗策略开辟道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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