Effective Permeation of Anticancer Drugs into Glioblastoma Spheroids via Conjugation with a Sulfobetaine Copolymer

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Abstract

Three-dimensional cell aggregates (spheroids) are becoming a research focus because their construction is similar to that in vivo microenvironments, enabling the acceleration of drug discovery and reducing the need for animal tests, and other advantages. However, the delivery of drugs to the inside of spheroids is time-consuming and has low efficiency. In this study, we selected a sulfobetaine copolymer that translocates to the cell membrane in monolayer cultured cells as a nanocarrier of anticancer drugs. Doxorubicin (Dox) and 17-demethoxy-17-allylamino geldanamycin (17AAG) were modified to the copolymer of sulfobetaine methacrylate and poly(ethylene glycol) methacrylate, P(SB-PEG), and added to glioblastoma A-172 cell spheroids. Dox-P(SB-PEG) showed fast permeation into A-172 spheroids, and the fluorescence in cells was observed in the center area of the spheroids within 1 h of polymer addition. Conversely, only the outer one to two cell layers of spheroids were observed when Dox was added to the spheroids. Dox-P(SB-PEG) in A-172 spheroids was localized in the mitochondria of each cell and exhibited comparable drug efficacy to that of Dox in growth inhibition assays of A-172 spheroids. Moreover, approximately 10-fold higher drug efficacy in growth inhibition and invasion of A-172 spheroids was found using 17AAG-P(SB-PEG). Conjugating anticancer drugs with P(SB-PEG) is a promising strategy to enhance drug permeation and efficacy against spheroid cells.

Original languageEnglish
Pages (from-to)5044-5052
Number of pages9
JournalBiomacromolecules
Volume21
Issue number12
DOIs
Publication statusPublished - 2020 Dec 14

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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