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Lookup NU author(s): Professor Moein MoghimiORCiD
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© 2015 American Chemical Society. 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 (1-5 kDa), H-PLLs (15-30 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.
Author(s): Hall A, Wu L-P, Parhamifar L, Moghimi SM
Publication type: Article
Publication status: Published
Online publication date: 08/06/2015
Acceptance date: 01/01/1900
ISSN (print): 1525-7797
ISSN (electronic): 1526-4602
Publisher: American Chemical Society
PubMed id: 26053306
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