Supramolecular crafting of self-assembling camptothecin prodrugs with enhanced efficacy against primary cancer cells

Hao Su, Pengcheng Zhang, Andrew G. Cheetham, Jin Mo Koo, Ran Lin, Asad Masood, Paula Schiapparelli, Alfredo Quiñones-Hinojosa, Honggang Cui

Research output: Contribution to journalArticle

Abstract

Chemical modification of small molecule hydrophobic drugs is a clinically roven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubility while maintaining high potency against cancer cells. We found that camptothecin (CPT) prodrugs created by conjugating two CPT molecules onto a hydrophilic segment can associate into filamentous nanostructures in water. Our results suggest that these SAPD exhibit much greater efficacy against primary brain cancer cells relative to that of irinotecan, a clinically used CPT prodrug. We believe these findings open a new avenue for rational design of supramolecular prodrugs for cancer treatment.

Original languageEnglish (US)
Pages (from-to)1065-1074
Number of pages10
JournalTheranostics
Volume6
Issue number7
DOIs
StatePublished - Jan 1 2016

Keywords

  • Brain cancer
  • CPT Prodrug
  • High potency
  • Nanomedicine
  • Peptides
  • Self-assembly

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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  • Cite this

    Su, H., Zhang, P., Cheetham, A. G., Koo, J. M., Lin, R., Masood, A., Schiapparelli, P., Quiñones-Hinojosa, A., & Cui, H. (2016). Supramolecular crafting of self-assembling camptothecin prodrugs with enhanced efficacy against primary cancer cells. Theranostics, 6(7), 1065-1074. https://doi.org/10.7150/thno.15420