Aggregation and pH Responsive Disassembly of a New Acid-Labile Surfactant Synthesized by Thiol−Acrylate Michael Addition Reaction

Abstract

Nucleophilic thiol-acrylate Michael reaction between a hydrophobic thiol and hydrophilic acrylate derivative generated a nonionic surfactant with acid-labile β-thiopropionate linker. Micellization of the surfactant, its ability to encapsulate hydrophobic dye, acid-induced disruption of the aggregate and pH-selective dye release profile have been revealed in this report. The micellar aggregates were found to be stable under neutral conditions, but they could be disrupted in acidic pH (5.3), and thus the encapsulated hydrophobic dye molecules could be selectively released. Appropriate control experiments revealed that the sulfur atom in the β-position is essential for acidic hydrolysis of the ester functionality of the surfactant.

Unlocking a Caged Lysosomal Protein from a Polymeric Nanogel with a pH Trigger

“…The absence of the β-thiopropionate functionality removes the pH trigger from the nanogel. 52 Encapsulation of GAA in this control nanogel was achieved using a method similar to the one above (see Experimental Section for details). The control nanogel’s encapsulation efficiency was ∼50%, as assessed by the BCA assay.…”

Stimuli-Responsive Polymeric Nanocarriers as Promising Drug and Gene Delivery Systems

“…It is also important to note that the drug release profile of this kind of pH-responsive cleavable nanocarriers is dependent on the rate of hydrolysis of acid-labile bonds. For example, micellar aggregates and polymersomes with acid-labile b-thiopropionate linker have shown sustained release of the encapsulated molecules due to the slow acid-induced hydrolysis (Dan et al 2010;Dan and Ghosh 2013). Thus, drug release rate from the micelles can be tuned by selecting appropriate acid-labile linkers.…”

Lipase-catalyzed synthesis of acid-degradable poly(β-thioether ester) and poly(β-thioether ester-co-lactone) copolymers

“…The b-thiopropionate groups in their polymer backbone can be hydrolyzed selectively under mild acidic conditions (pH~5.5) at a very slow rate [18,19] unlike other aciddegradable functional groups, such as orthoester, acetal, ketal, and hydrazine groups, which show much faster degradation kinetics [6,20]. This feature of the b-thiopropionate group is highly relevant in the control release of drug selectively in tumor cells, which have a more acidic environment than normal cells [20e22].…”