Cover Feature: Cyclic Disulfide Liposomes for Membrane Functionalization and Cellular Delivery (Chem. Eur. J. 45/2022)

Abstract

Multifunctional: Cyclic disulfide liposomes have been developed for the dual purposes of enhancing cellular delivery through reaction with cell‐surface thiols and facilitating liposome functionalization. These liposomes are depicted in the form of beach balls being lofted at their target cells: a scene of a warm day at the beach for a summertime issue of Chemistry—A European Journal. More information can be found in the Research Article by M. D. Best and co‐workers (DOI: 10.1002/chem.202201164).

Asparagusic Acid – A Unique Approach toward Effective Cellular Uptake of Therapeutics: Application, Biological Targets, and Chemical Properties

“…Among different 1,2‐dithiolanes, asparagusic acid activity is the highest, demonstrating fast and reliable dynamic covalent exchange with TFRC and further cytosolic transit into deep tissue [76,77] . The enhanced liposome delivery decorated with asparagusic acid to mammary adenocarcinoma cells was observed, which makes the application of asparagusic acid moiety very promising in production of efficient therapeutic cargo for cancer therapy [78] …”

Sticking the Landing: Enhancing Liposomal Cell Delivery using Reversible Covalent Chemistry and Caged Targeting Groups

“…For example, Du and co-workers developed lipids containing disulfide groups within their acyl chains that were shown to release cargo upon treatment with dithiothreitol. [27] We have explored cyclic disulfide lipids (CDLs) 7 a-b (Figure 6A) [10] as a means for exploiting thiols presented on cell surfaces [28] for driving cell entry as well as for facilitating the decoration of liposome surfaces with functional groups. To confirm thiol reactivity and liposome derivatization, we developed an assay in which reaction with biotin-thiol conjugates enforced the immobilization of 7 a-b onto streptavidin-coated microplates, which validated dose-dependent anchoring based on the percentage of 7 a-b included within liposomes (Figure 6B).…”

“…One approach has entailed platforms designed to undergo reversible covalent chemistry with partner reactive groups presented on cell surfaces in a manner that engages liposomes to encourage cell entry. In this realm, we will discuss boronic acid liposomes for binding to cell‐surface glycans [9] as well as cyclic disulfide liposomes for conjugation to thiol groups presented on membranes [10] . Additionally, to enhance control over cationic liposomal systems, we have recently reported liposomes that initially present neutral caged guanidine moieties that are thus silent in terms of cell entry [11] .…”

“…In this realm, we will discuss boronic acid liposomes for binding to cell-surface glycans [9] as well as cyclic disulfide liposomes for conjugation to thiol groups presented on membranes. [10] Additionally, to enhance control over cationic liposomal systems, we have recently reported liposomes that initially present neutral caged guanidine moieties that are thus silent in terms of cell entry. [11] However, upon encountering a trigger known to be upregulated in diseased cells, reactive oxygen species (ROS), the cationic guanidinium group is unveiled and cell entry is activated.…”

Copper-responsive liposomes for triggered cargo release employing a picolinamide−lipid conjugate

“…Through recent advances in the field, the enhanced abundance of chemical agents at diseased sites compared to healthy cells and tissues has emerged as a phenomenon that can be exploited for controlled cargo release or activated cell delivery. [6][7][8][9][10][11][12] A few metal ion-responsive liposome platforms have been developed in this context. For example, Zefirov and co-workers reported a bispidinone-based copper-responsive molecular switch to trigger liposomal content release.…”