Study On In-situ Polymerization Induced Self-assembly Behavior Of Bovine Serum Albumin Via Photoinitiated RAFT Polymerization

In recent years,the development of polymerization-induced self-assembly(PISA)technology has become a versatile,one-pot strategy to synthesize block copolymer nanomaterials,which conducted at high polymer concentrations.However,protein-based self-assembled nano-objects have attracted much attention due to their great biocompatibility and degradability as well as highly sophisticated functions which have showed broad applications in drug/gene delivery,protein theraphy,nanoreactors,or artificial cells etc.Considering the very fragile structure of the protein,it is difficult to carry out the reaction at high temperature in the traditional PISA method.Therefore,it is very meaningful to study the PISA of proteins.In this study,we show a facile and efficient way to synthesize protein-based nanoparticles by taking advantage of photo-initiated RAFT polymerization induced self-assembly by using multi-RAFT modified bovine serum albumin(BSA)as a macro-RAFT agent.1.Synthesis of a macromolecule chain transfer agent based on bovine serum albumin(BSA-CTA).We designed and synthesized a mercaptothiazoline-activated RAFT agent,and then synthesized BSA-CTA by reacting the amino groups on the surface of BSA with mercaptothiazoline at the H2O/DMSO interface.And we calculated the number of RAFT agent on the surface of BSA via UV-vis spectroscopy and MALDI-TOF MS.2.The self-assembly of BSA was achieved via in-situ photoinitiated polymerization induced self-assembly to obtain spherical protein nanoparticles.And the morphology and size of nanoparticles,the molecular of polymer and polymer dispersity index(PDI)were analyzed by SEM,TEM,DLS and GPC.Under different experimental conditions,we still can obtain sphere nanoparticles with the size of 164-255 nm.3.The mechanism of polymerization-induced self-assembly of BSA was explored.The growth of the PHPMA chains results in the increase of the hydrophobicity of the star BSA-PHPMA conjugates,and when reaching the critical aggregation concentration in aqueous solution,they will aggregate into nanoparticles via the hydrophobic interaction of PHPMA.4.We confirmed the stability,low cytotoxicity and high enzyme activity of BSA sphere nanoparticles.And through the encapsulation effect to achieve the load of different types of substances,including fluorescence dyes Nile red,small molecule drugs DOX and biomacromolecules DNA.