Using membrane composition to fine-tune the pK_a of an optical liposome pH sensor

Abstract

Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe pKa is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe pKa in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe pKa values by < 1 unit. The results show that rational modification of the membrane composition is a general non-covalent way to fine-tune the pKa of an optical liposome sensor for optimal pH sensing performance.

Unsymmetrical pentamethine cyanines for visualizing physiological acidities from the whole-animal to the cellular scale with pH-responsive deep-red fluorescence

“…2,3,3-Trimethyl-3H-indole first reacted with 1 to give intermediate 2, which further reacted with N-substituted indoles 3a–f to afford the final products DR1–6. In this way, the desired products were obtained with higher overall yields (42%) compared to that (yield: 7%) obtained using the adverse condensation sequence reported by Clear et al 19 ( Scheme 2b ). This experimental result can be attributed to the different reactivities of N-substituted and non-N-substituted indoles.…”

Solvatochromic and Acid–Base Molecular Probes in Surfactant Micelles: Comparison of Molecular Dynamics Simulation with the Experiment

“…In addition to such small molecules, large-sized ones are also used in study loidal and biocolloidal systems. For instance, relatively recently, Clear et al [190] polymethine dyes (Scheme 9) as optical liposome pH sensors: In addition to such small molecules, large-sized ones are also used in studying colloidal and biocolloidal systems. For instance, relatively recently, Clear et al [190] applied polymethine dyes (Scheme 9) as optical liposome pH sensors: In addition to such small molecules, large-sized ones are also used in studying colloidal and biocolloidal systems.…”

“…For instance, relatively recently, Clear et al [190] polymethine dyes (Scheme 9) as optical liposome pH sensors: In addition to such small molecules, large-sized ones are also used in studying colloidal and biocolloidal systems. For instance, relatively recently, Clear et al [190] applied polymethine dyes (Scheme 9) as optical liposome pH sensors: In addition to such small molecules, large-sized ones are also used in studying colloidal and biocolloidal systems. For instance, relatively recently, Clear et al [190] applied polymethine dyes (Scheme 9) as optical liposome pH sensors:…”

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

“…Another factor determining stability, is RNA length which is calculated to be inversely correlated with stability against hydrolysis [ 3 ]. Attempts at fortification of mRNA stability employing lipid pharmacotechnic formulations are to be considered carefully: utilization of lipids whose cationic head group can lower the pKa of the 2-hydroxyl group residing on the ribose moiety of the mRNA are best avoided since even a 2-unit shift can significantly hasten mRNA hydrolysis [ 185 , 186 ].…”