Polypept(o)ide Based Biodegradable Cylindrical Polymer Brushes: Controlling Size, Shape, Surface Functionality, and Stability

ACS Applied Materials & Interfaces, vol. 17, pp. 62969–62982

Abstract

High Resolution Image Download MS PowerPoint Slide Cylindrical polymer brushes (CPBs) enable remarkable control over nanoparticle properties solely through sequential polymerization. The spatial dimensions and functionality of the resulting polymeric nanoparticles can be adjusted by the ratio of backbone to side chain length and the chemical nature of both parts. In this work, we present a convenient and straightforward synthetic pathway to polypept(o)ide-based CPBs using a “grafting-from” strategy utilizing poly- l -lysine (pLys) as the macroinitiator backbone and polysarcosine (pSar) as the side chain. End-capping of pSar chains with azido-butyric acid pentafluorophenyl ester enables facile surface functionalization by click chemistry (e.g., dye labeling). This strategy allows for straightforward control over nanoparticle size ( R h from 12 to 41 nm), shape (aspect ratio from 1.7 to 8.3), and molecular weights (from 350 to 2980 kg mol –1 ). Despite the high grafting density of pSar side chains from the pLys backbone (>85%), enzymatic degradation is feasible by the natural protease B from Streptomyces griseus and enables the analysis of pSar side chains upon cleavage ( Đ = 1.03–1.04). Interestingly, these CPBs exhibit thermal stability in phosphate-buffered saline at elevated temperatures (60 °C for 24 h) and display notable circulation in zebrafish embryos (up to 3 days). Therefore, CPBs based on polypept(o)ides not only allow for precise tuning of size, shape, and surface functionality but also display high biocompatibility and extended circulation time in zebrafish, leveraging the stealth-like properties of pSar.

Authors 11

1. Christine Ilona Seidl Aachen Leiden Academic Centre for Drug Research

   Leiden University · Johannes Gutenberg University Mainz · 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, Mainz 55131, Germany

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

2. Bonan Zhao Aachen Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

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

3. Rüdiger Berger

   Max Planck Institute for Polymer Research

   Affiliation as printed

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

4. Lin Jian

   Max Planck Institute for Polymer Research

   Affiliation as printed

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

5. Kaloian Koynov

   Max Planck Institute for Polymer Research

   Affiliation as printed

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

6. Meike Gangluff

   Johannes Gutenberg University Mainz · BioNTech (Germany)

   Affiliation as printed

   BioNTech SE, An der Goldgrube 12, Mainz 55131, Germany

   Department Chemie, Johannes Gutenberg University Mainz, Duesbergweg 10-14, Mainz 55131, Germany

7. Rivka Fontijn Aachen Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

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

8. Lu Su Aachen Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

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

9. Jeroen Bussmann Aachen Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

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

10. Heyang Zhang Aachen Leiden Academic Centre for Drug Research

    Leiden University

    Affiliation as printed

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

11. Matthias Barz corresponding Aachen Leiden Academic Centre for Drug Research

    Leiden University · Johannes Gutenberg University Mainz · 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, Mainz 55131, Germany

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