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Asymetric Triblock Copolymer Nanocarriers for Controlled Localization and pH-Sensitive Release of Proteins
Journal
Langmuir
Volume
32
Number
40
Pages / Article-Number
10235-10243
Mesh terms
Animals; Cattle; Drug Carriers, toxicity; Drug Liberation; HeLa Cells; Humans; Hydrogen-Ion Concentration; Nanoparticles, chemistry; Particle Size; Polyesters, toxicity; Polyethylene Glycols, toxicity; Polymethacrylic Acids, toxicity; Serum Albumin, Bovine, chemistry; Sphingomyelin Phosphodiesterase, chemistry; Surface Properties; Temperature
Abstract
Designing nanocarriers to release proteins under specific conditions is required to improve therapeutic approaches, especially in treating cancer and protein deficiency diseases. We present here supramolecular assemblies based on asymmetric poly(ethylene glycol)-b-poly(methylcaprolactone)-b-poly(2-(N,Ndiethylamino)ethyl methacrylate) (PEG-b-PMCL-b-PDMAEMA) copolymers for controlled localization and pH-sensitive release of proteins. Copolymers self-assembled in soft nanoparticles with a core domain formed by PMCL, and a hydrophilic domain based on PEG mainly embedded inside, and the branched PDMAEMA exposed at the particle surface. We selected as model proteins to be attached to the nanoparticles bovine serum albumin (BSA) and acid sphingomyelinase (ASM), the latter being an ideal candidate for protein replacement therapy. The hydrophilic/hydrophobic ratio, nanoparticle size, and the nature of biomolecules are key factors for modulating protein localization and attachment efficiency. The predominant outer shell of PDMAEMA allows efficient pH-triggered release of BSA and ASM, and in acidic conditions >70% of the bound proteins were released. Uptake of protein-attached nanoparticles by HELA cells, together with low toxicity and pH-responsive release, supports such protein-bound nanoparticles as efficient stimuli-responsive candidates for protein therapy.
