Polypept(o)ide-Based Core-Shell Bottlebrush Polymers: A Versatile Platform for Drug Encapsulation

Cylindrical bottlebrush polymers (CBPs) enable the precise adjustment of nanoparticle properties such as size, shape, and functionality exclusively by polymer synthesis. In addition, block copolymer side chains enable direct access to core-shell structure. In this study, the synthesis of polypept(o)ides-based core-shell CBPs is presented through a "grafting-from" strategy. While, poly-lysine (pLys) serves as the backbone, poly(γ-benzyl-l-glutamic acid)-block-polysarcosine (pGlu(OBn)-b-pSar) copolymers form the side chains. This approach enables the synthesis of core-shell nanoparticles, referred as core-shell brushes (CSBs), with hydrodynamic radius (R_h) from 17 to 70 nm, and molecular weights (1320-4000 kg mol^-1) with dispersity indices ≈1.3 as determined by size-exclusion chromatography. Dasatinib is chosen as a drug molecule model to explore the potential of such synthetical CSBs as a platform for drug encapsulation by π-π-interactions. An overall loading efficiency of 10% is achieved, which also displayed sustained release within 72 h, cellular uptake into human glioblastoma (U-87 MG) cells, and drug-related therapeutic efficacy. While drug release can be further optimized by covalent drug attachment, these results establish a strong foundation for the use of CSBs in nanomedicine.