Asymmetric Triblock Copolymer Nanocarriers for Controlled Localization and pH-Sensitive Release of Proteins.
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.
Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Daniela
D
Vasquez
Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Tomaz
T
Einfalt
Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Wolfgang
W
Meier
Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Cornelia G
CG
Palivan
D000818:Animals; D002417:Cattle; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
D004337:Drug Carriers; D011091:Polyesters; D011109:Polymethacrylic Acids; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D013108:Sphingomyelin Phosphodiesterase