Superior HyperCEST Performance of Membrane-Anchored Xenon Hosts in Nanocarriers with Variable Membrane Fluidity

Motivation: The efficiency of CEST agents for hyperpolarized 129Xe depends on the exchange rate of Xe in/out of tailored host structures. For liposomal designs, this may be influenced by the phospholipid membrane fluidity. Goal(s): This study investigates how cholesterol, which is often added for liposome stability, impacts the HyperCEST performance. Approach: We compared the changes in CEST buildup from liposomes with variable cholesterol content and either membrane-anchored (i.e., lipopeptide-based) or freely diffusing Xe host. Results: The HyperCEST efficiency for membrane-anchored Xe hosts is much less sensitive to membrane stiffening than for unbound hosts. Lipopeptide-based HyperCEST agents are thus a powerful approach for biosensor design. Impact: The HyperCEST performance of membrane-anchored xenon hosts in liposomal nanocarriers shows reduced susceptibility to membrane stiffening compared to non-functionalized hosts. These less susceptible lipopeptide-based hosts are thus the preferred approach for future in vivo applications.