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

Macromolecular Bioscience, vol. 25, pp. e2500083

Abstract

Abstract 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 (Rh) 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.

Authors 6

1. Bonan Zhao Aachen

   Leiden University

   Affiliation as printed

   Leiden Academic Center for Drug Research (LACDR) Leiden University Einsteinweg 55 Leiden 2333CC The Netherlands

2. Rüdiger Berger

   Max Planck Institute for Polymer Research

   Affiliation as printed

   Physics at Interfaces Max Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz Germany

3. Lin Jian

   Max Planck Institute for Polymer Research

   Affiliation as printed

   Physics at Interfaces Max Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz Germany

4. Kaloian Koynov

   Max Planck Institute for Polymer Research

   Affiliation as printed

   Physics at Interfaces Max Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz Germany

5. Heyang Zhang corresponding Aachen

   Leiden University

   Affiliation as printed

   Leiden Academic Center for Drug Research (LACDR) Leiden University Einsteinweg 55 Leiden 2333CC The Netherlands

6. Matthias Barz corresponding Aachen

   Leiden University · University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Dermatology University Medical Center of the Johannes Gutenberg University Mainz Langenbeckstraße 1 55131 Mainz Germany

   Leiden Academic Center for Drug Research (LACDR) Leiden University Einsteinweg 55 Leiden 2333CC The Netherlands