Caspofungin Functionalized Polymethacrylates with Antifungal Properties

Biomacromolecules. 2020 Jun 8;21(6):2104-2115. doi: 10.1021/acs.biomac.0c00096. Epub 2020 May 13.


We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PmPEGMA) and hydrophobic poly(methyl methacrylate) (PMMA) caspofungin conjugates by a post-polymerization modification of copolymers containing 10 mol % pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition-fragmentation chain transfer copolymerization. The coupling of the clinically used antifungal caspofungin was confirmed and quantified in detail by a combination of 1H-, 19F- and diffusion-ordered NMR spectroscopy, UV-vis spectroscopy, and size exclusion chromatography. The trifunctional amine-containing antifungal was attached via several amide bonds to the hydrophobic PMMA, but sterical hindrance induced by the mPEGMA side chains prohibited intramolecular double functionalization. Both polymer-drug conjugates revealed activity against important human-pathogenic fungi, that is, two strains of Aspergillus fumigatus and one strain of Candida albicans (2.5 mg L-1 < MEC < 8 mg L-1, MIC50 = 4 mg L-1), whereas RAW 264.7 macrophages as well as HeLa cells remained unaffected at these concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents* / pharmacology
  • Caspofungin
  • HeLa Cells
  • Humans
  • Polymethacrylic Acids*


  • Antifungal Agents
  • Polymethacrylic Acids
  • polymethacrylic acid
  • Caspofungin