Monitoring the Collapse of pH-Sensitive Liposomal Nanocarriers and Environmental pH Simultaneously: A Fluorescence-Based Approach

Abstract

Nowadays, the encapsulation of therapeutic compounds in so-called carrier systems is a very smart method to achieve protection as well as an improvement of their temporal and spatial distribution. After the successful transport to the point of care, the delivery has to be released under controlled conditions. To monitor the triggered release from the carrier, we investigated different fluorescent probes regarding their response to the pH-induced collapse of pH-sensitive liposomes (pHSLip), which occurs when the environmental pH falls below a critical value. Depending on the probe, the fluorescence decay time as well as fluorescence anisotropy can be used equally as key parameters for monitoring the collapse. Especially the application of a fluorescein labeled fatty acid (fPA) enabled the monitoring of the pHSLips collapse and the pH of its microenvironment simultaneously without interference. Varying the pH in the range of 3 < pH < 9, anisotropy data revealed the critical pH value at which the collapse of the pHSLips occurs. Complementary methods, e.g., fluorescence correlation spectroscopy and dynamic light scattering, supported the analysis based on the decay time and anisotropy. Additional experiments with varying incubation times yielded information on the kinetics of the liposomal collapse.

Copper Complex Nanoformulations Featuring Highly Promising Therapeutic Potential in Murine Melanoma Models

“…These data support the rational for using F6 as a tool for liposomal Cuphen release at the mildly acidic tumour microenvironment. The same effect has been reported for the widely described pH-sensitive lipid composition based on a fusogenic phospholipid, dioleoyl phosphatidyl ethanolamine (DOPE), in combination with CHEMS [39,41].…”

“…Conversely, F4 did not display such behavior, as no statistically significant differences were observed for the three tested . Moreover, the protonation of CHEMS at pH ranging from 4.5 to 6.5 has been described [39]. These data support the rational for using F6 as a tool for liposomal Cuphen release at the mildly acidic tumour microenvironment.…”

“…A second series of pH-sensitive nanoformulations (F5, F6 and F7) was developed to explore Cuphen release at the slightly acidic tumour microenvironment [28,29]. To attain this goal, CHEMS was included in the lipid composition since, when in contact with an acidic milieu, it becomes protonated, leading to bilayer disruption and subsequent drug release [29,[39][40][41].…”

“…Tumours' microenvironment, as in the case of melanoma, is slightly acidic, presenting pH values around 6, in contrast to the normal physiological pH of 7.4 [28,29], which heavily impacts cancer development [47,48], and it can be explored as stimuli for triggering local liposomal drug release. In the current work, we developed long circulating pH-sensitive nanoliposomes by including CHEMS in the lipid composition [29,[39][40][41]. To validate pH-sensitive properties of F6, the quantification of the metallodrug still associated to nanoliposomes was assessed upon exposure to different pH conditions.…”

Enhanced non-viral gene delivery by coordinated endosomal release and inhibition of β-tubulin deactylase

“…As predicted, the addition of pH sensitive DOPE/CHEMS (20) resulted in significant augmentation of transfection efficiency in differentiated neurons (Figure 2). Confocal microscopy of labelled DNA (Supplementary Data) revealed the effect of DOPE/CHEM in facilitating the escape from these acidic compartments.…”