Reversibly PEGylated nanocarrier for cisplatin delivery

A star-shaped copolymer bearing a shell of poly(ethylene glycol) (PEG) chains was designed as a carrier of cisplatin. The proposed strategy was based on synthesis of a PEGylating agent and the incorporation of cisplatin as a reversible linker for PEG modification of the star macromolecules. The attachment of PEG chains to the stars and their release under physiological conditions, as well as the changes in particle size and mobility upon drug loading, was evidenced by diffusion ordered NMR spectroscopy (DOSY). The results demonstrated that PEGylation reduced inter-stars cross-linking and increased the stability of the nanocolloidal solution. The formation of PEG shell resulted in higher drug payload and improved drug release profile of the nanoconjugates. The in vitro bioassay in a panel of human tumor cell lines confirmed that the PEGylated conjugates exhibited superior growth inhibitory activity compared to the cisplatin-loaded nonPEGylated carrier.

PEGylated core–shell type star macromolecular nanocarrier of cisplatin (left) and its DOSY NMR spectrum (right), evidencing the attachment of PEG chains to the stars.Figure optionsDownload as PowerPoint slideHighlights
► Nanocarrier of cisplatin with a releasable PEG shell was designed.
► Cisplatin was used as reversible linker for PEG attachment to the star-shaped carrier.
► PEGylated nanoconjugates were characterized via diffusion ordered NMR spectroscopy.
► The PEGylated conjugates displayed improved features as cisplatin delivery system.