Differential Modulation of Cellular Bioenergetics by Poly(l-lysine)s of Different Molecular Weights

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• 作者：Arnaldur Hall ; Lin-Ping Wu ; Ladan Parhamifar ; Seyed Moein Moghimi
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：July 13, 2015
• 年：2015
• 卷：16
• 期：7
• 页码：2119-2126
• 全文大小：527K
• ISSN：1526-4602

文摘

Poly(l-lysine)s (PLLs), and related derivatives, have received considerable attention as nonviral vectors. High molecular weight PLLs (H-PLLs) are superior transfectants compared with low Mw PLLs (L-PLLs), but suggested to be more cytotoxic. Through a pan-integrated metabolomic approach using Seahorse XF technology, we studied the impact of PLL size on cellular bioenergetic processes in two human cell lines. In contrast to L-PLLs (1鈥? kDa), H-PLLs (15鈥?0 kDa) were more detrimental to both mitochondrial oxidative phosphorylation (OXPHOS) and glycolytic activity resulting in considerable intracellular ATP depletion, thereby initiating necrotic-type cell death. The cellular differences to polycation sensitivity were further related to the mitochondrial state, where the impact was substantial on cells with hyperpolarized mitochondria. These medium-throughput approaches offer better opportunities for understanding inter-related intracellular and cell type-dependent processes instigating a bioenergetics crisis, thus, aiding selection (from available libraries) and improved design of safer biodegradable polycations for nucleic acid compaction and cell type-specific delivery.