Hydrogen Bond Strength-Mediated Self-Assembly of Supramolecular Nanogels for Selective and Effective Cancer Treatment

Fasih Bintang Ilhami, Ya Tang Yang, Ai Wei Lee, Yu Hsuan Chiao, Jem Kun Chen, Duu Jong Lee, Juin Yih Lai, Chih Chia Cheng

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

This study provides a significant contribution to the development of multiple hydrogen-bonded supramolecular nanocarrier systems by demonstrating that controlling the hydrogen bond strength within supramolecular polymers represents a crucial factor to tailor the drug delivery performance and enhance the effectiveness of cancer therapy. Herein, we successfully developed two kinds of poly(ethylene glycol)-based telechelic polymers Cy-PEG and UrCy-PEG having self-constituted double and quadruple hydrogen-bonding cytosine (Cy) and ureido-cytosine (UrCy) end-capped groups, respectively, which directly assemble into spherical nanogels with a number of interesting physical characteristics in aqueous solutions. The UrCy-PEG nanogels containing quadruple hydrogen-bonded UrCy dimers exhibited excellent long-term structural stability in a serum-containing biological medium, whereas the double hydrogen-bonded Cy moieties could not maintain the structural integrity of the Cy-PEG nanogels. More importantly, after the drug encapsulation process, a series of in vitro experiments clearly confirmed that drug-loaded UrCy-PEG nanogels induced selective apoptotic cell death in cancer cells without causing significant cytotoxicity to healthy cells, while drug-loaded Cy-PEG nanogels exerted nonselective cytotoxicity toward both cancer and normal cells, indicating that increasing the strength of hydrogen bonds in nanogels plays a key role in enhancing the selective cellular uptake and cytotoxicity of drugs and the subsequent induction of apoptosis in cancer cells.

Original languageEnglish
Pages (from-to)4446-4457
Number of pages12
JournalBiomacromolecules
Volume22
Issue number10
DOIs
Publication statusPublished - Oct 11 2021

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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