Lipid Switches: Stimuli‐Responsive Liposomes through Conformational Isomerism Driven by Molecular Recognition

Abstract

Advancements in the field of liposomal drug carriers have culminated in greatly improved delivery properties. An important aspect of this work entails development of designer liposomes for release of contents triggered by environmental changes. The majority of these systems are driven by chemical reactions in the presence of different stimuli. However, a promising new paradigm instead focuses on molecular recognition events as the impetus for content release. In certain cases, these platforms exploit synthetic lipid switches designed to undergo conformational changes upon binding to target ions or molecules that perturb membrane assembly, thereby triggering cargo release. Examples of this approach reported thus far showcase how rational design of lipid switches can result in dramatic changes in lipid assembly properties. These strategies show great promise for opening up new pathophysiological stimuli that can be harnessed for programmed content release in drug delivery applications.

Bombesin receptor-targeted liposomes for enhanced delivery to lung cancer cells

“…Future studies on cystabn-targeted liposomal carriers will examine the uptake and trafficking of these nanocarriers, particularly with regards to their efficiency of carrying chemotherapeutic agents into the cell. Poor intracellular accumulation of nanocarriers can be improved through targeted and triggered drug release, for example through the incorporation of temperaturesensitive [32] or light-sensitive lipids [33]. These approaches have shown promise in enhancing the cellular/tumoural accumulation of chemotherapeutic agents in various models [34,35].…”

Exploration of trans‐2‐(azaarylsulfanyl)‐cyclohexanols as potential pH‐triggered conformational switches

“…Conformational or mechanical molecular switches are molecular systems able to perform a directed change in the relative orientation of their parts under external stimulus (light, radiation, electric field, metal complex formation, pH change, etc). They play a central role in a design of controllable compounds, molecular machinery, and intelligent materials with a variety of possible applications including drug release, new sensor techniques, or information storage and transmission . The cyclohexane‐based molecular systems provide an efficient prototype for such switches .…”

“…The variation of amino groups allows a broad tuning of the conformational equilibrium, and the basicity of amino functions could be adjusted for a conformational response within a selected range of pH . Other cyclic and noncyclic scaffolds and more complex molecular devices were also suggested recently as pH‐sensitive conformational switches for similar applications …”

Easy Formation of Functional Liposomes in Water Using a pH‐Responsive Microbial Glycolipid: Encapsulation of Magnetic and Upconverting Nanoparticles

“…Lipid switches were recently combined with classical phospholipid liposomes to deliver a cargo upon application of an external stimulus (pH, ion). In this paper, we take inspiration of this concept to develop a fully water‐based (at nearly neutral pH) bulk phase‐change method to encapsulate, rather than release, a cargo composed of metastable colloids into vesicles.…”

“…Non-equilibrium encapsulation is generally obtained in food and material science through dynamic processes such as spray drying, [26,27] while recent theoretical work could explore its possibilities in the compartimentalization within elastic geometries like carboxysomes. [28] Lipid switches [29,30] were recently combined with classical phospholipid liposomes to deliver a cargo upon application of an external stimulus (pH, ion). In this paper, we take inspiration of this concept to develop a fully water-based (at nearly neutral pH) bulk phase-change method to encapsulate, rather than release, a cargo composed of metastable colloids into vesicles.…”