Bioorthogonal, two-component delivery systems based on antibody and drug-loaded nanocarriers for enhanced internalization of nanotherapeutics

Sudath Hapuarachchige, Wenlian Zhu, Yoshinori Kato, Dmitri Artemov

Research output: Contribution to journalArticlepeer-review

Abstract

Nanocarriers play an important role in targeted cancer chemotherapy. The optimal nanocarrier delivery system should provide efficient and highly specific recognition of the target cells and rapid internalization of the therapeutic cargo to reduce systemic toxicity as well as to increase the cytotoxicity to cancer cells. To this end, we developed a two-step, two-component targeted delivery system based on antibody and drug-loaded nanocarrier that uses bioorthogonal click reactions for specific internalization of nanotherapeutics. The pretargeting component, anti-HER2 humanized monoclonal antibody, trastuzumab, functionalized with azide groups labels cancer cells that overexpress HER2 surface receptors. The drug carrier component, dibenzylcyclooctyne substituted albumin conjugated with paclitaxel, reacts specifically with the pretargeting component. These two components form cross-linked clusters on the cell surface, which facilitates the internalization of the complex. This strategy demonstrated substantial cellular internalization of clusters consisted of HER2 receptors, modified trastuzumab and paclitaxel-loaded albumin nanocarriers, and subsequent significant cytotoxicity in HER2-positive BT-474 breast cancer cells. Our results show high efficacy of this strategy for targeted nanotherapeutics. We foresee to broaden the applications of this strategy using agents such as radionuclides, toxins, and interfering RNA.

Original languageEnglish (US)
Pages (from-to)2346-2354
Number of pages9
JournalBiomaterials
Volume35
Issue number7
DOIs
StatePublished - Feb 2014

Keywords

  • Bioorthogonal click chemistry
  • Drug delivery
  • Nanocarriers
  • Targeted therapy

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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