Controlled Release of a Micelle Payload via Sequential Enzymatic and Bioorthogonal Reactions in Living Systems

Abstract

Abioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology,w ed eveloped an ew generation of cleavable micelles able to disassemble through as equential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery

“…The hydrophobic part of the polymer comprises the core of NPs, and the coating of PEG is the outer layer of particles. The researchers have also synthesized the fluorescence-labeled polymers sensitive to light, enzymes, temperatures, pH, ultrasound, or redox to prepare PEGylated NPs to improve drug delivery and bioimaging [36][37][38][39][40][41][42][43] . The different copolymers are selected to prepare NPs with other functions and provide very high surface graft density under self-assembly strategies.…”

“…The different copolymers are selected to prepare NPs with other functions and provide very high surface graft density under self-assembly strategies. However, the synthesis of these copolymers is relatively complex and requires precise operation and reasonable condition control 38 . Also, studies have shown that the polymeric NPs prepared by emulsification have higher PEG coverage than those by nanoprecipitation 44,45 .…”

Strain‐Promoted 1,3‐Dithiolium‐4‐olates–Alkyne Cycloaddition

“…In recent years, sydnones and imino‐sydnones were identified as promising dipoles for strain‐promoted ligation with cyclooctynes . These transformations hold much promise for click and bioorthogonal chemistry and a variety of applications were reported in living cells and organisms …”

Bioorthogonal Ligations and Cleavages in Chemical Biology

“…[108] In 2019, the same group described the generation of cleavable micelles able to disassemble by using click-and-release technology via a sequential enzymatic and bioorthogonal activation process, and the results indicated that the method could be applied to deliver the substances encapsulated into micelles in living cells as well as in mice. [109] They also synthesized the group of substituted iminosydnones and explored the structure-activity relationship between the compounds and strain alkynes (Figure 22). [110] Very recently, Kolodych and Wagner achieved the synthesis of monodisperse antibody-conjugated drugs using the reaction of iminosydnones and ring strain alkynes.…”