Fabrication Of Janus-Type Amphiphilic Brush Copolymers As Drug Delivery Systems For Controlled Release

Janus polymers and nanoparticles with two distinctly incompatible faces are intriguing materials for both fundamental and practical investigations.However,the preparation of Janus nanoparticles generally requires sophisticated design of building segments and multi-step processing procedures.In this study,we reported a cyclic brush?cb?polymer-based novel strategy toward Janus polymers.A Janus-type amphiphilic cb copolymer with both hydrophilic oligo?ethylene glycol??OEG?and hydrophobic oligo??-caprolactone??OCL?brushes grafting from a cyclic core was designed and synthesized by a combination of atom transfer radical polymerization?ATRP?,intra-chain click cyclization,and ring-opening polymerization?ROP?techniques.Interestingly,the resulting Janus-type amphiphilic cb copolymers showed greater in vitro cytotoxicity relative to the bottlebrush?bb?analogues for anti-cancer drug delivery.The Janus-type amphiphilic cb copolymers developed herein thus represent a novel platform for controlled drug release.The details are listed as follows,1.Two bottlebrush-like amphiphilic block copolymers with the same composition and different oligo??-caprolactone?lengths were successfully synthesized by sequential ATRP reactions and ring-opening polymerization.The effect of bottlebrush structure on polymer properties and its potential biomedical applications as drug carriers were studied,and the relationship between structure and properties was summarized.It was found that the bb amphiphilic block copolymers form self-assembled micelles with the size of about 200 nm in water.The CMC value indicated that the longer the length of oligo??-caprolactone?in a certain range is,the more stable the thermodynamics is.And we concluded that the drug release at acidic conditions?pH 5.0?is faster than at pH 7.4.MTS cell viability assay showed the bottlebrush-like amphiphilic block copolymers have a small IC₅₀ value,so they have good potential as drug carriers.2.By concecutive ATRP reactions,intramolecular cyclization and ring-opening polymerization,the Janus-type amphiphilic cb copolymers with the same degree of polymerization of the bb analogues were successfully synthesized.We studied the influence of cyclic brush structure on polymer properties and its potential biomedical effects as drug carriers.In contrast to the bb analogues,the relationship between structure and performance was further summarized.The results revealed that the Janus-type amphiphilic cb copolymers form self-assembled micelles with the size of about 200 nm in water,and aren't significantly different from the bb analogues,but the CMC value indicated the bb analogues are more thermodynamically stable.The Janus-type amphiphilic cb copolymers have higher DLC and EE values than the bb analogues,and overall they have better drug-loading and drug release properties.MTS cell viability assay showed that the Janus-type amphiphilic cb copolymers have smaller IC₅₀ values than the bb analogues and show greater in vitro cytotoxicity.The cellular uptake study showed that the difference of the topological structure has no obvious effect on the endocytosis of drug-loaded micelles,so the origin of cytotoxicity is due to the difference in drug loading capacity.