Sadhukha Tanmoy, Wiedmann Timothy S, Panyam Jayanth
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Biomaterials. 2014 Sep;35(27):7860-9. doi: 10.1016/j.biomaterials.2014.05.085. Epub 2014 Jun 16.
Particle size is a key determinant of biological performance of sub-micron size delivery systems. Previous studies investigating the effect of particle size have primarily focused on well-dispersed nanoparticles. However, inorganic nanoparticles are prone to aggregation in biological environments. In our studies, we examined the consequence of aggregation on superparamagnetic iron oxide (SPIO) nanoparticle-induced magnetic hyperthermia. Here we show that the extent and mechanism of hyperthermia-induced cell kill is highly dependent on the aggregation state of SPIO nanoparticles. Well-dispersed nanoparticles induced apoptosis, similar to that observed with conventional hyperthermia. Sub-micron size aggregates, on the other hand, induced temperature-dependent autophagy through generation of oxidative stress. Micron size aggregates caused rapid membrane damage, resulting in acute cell kill. Overall, this work highlights the potential for developing highly effective anticancer therapeutics through designed aggregation of nano delivery systems.
粒径是亚微米级递送系统生物学性能的关键决定因素。以往研究粒径影响的主要集中在分散良好的纳米颗粒上。然而，无机纳米颗粒在生物环境中容易聚集。在我们的研究中，我们研究了聚集对超顺磁性氧化铁（SPIO）纳米颗粒诱导的磁热疗的影响。在此我们表明，热疗诱导细胞杀伤的程度和机制高度依赖于SPIO纳米颗粒的聚集状态。分散良好的纳米颗粒诱导细胞凋亡，类似于传统热疗所观察到的情况。另一方面，亚微米级聚集体通过产生氧化应激诱导温度依赖性自噬。微米级聚集体导致快速的膜损伤，从而导致急性细胞杀伤。总体而言，这项工作突出了通过设计纳米递送系统的聚集来开发高效抗癌疗法的潜力。
