Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis

Birju P. Shah, Nicholas Pasquale, Gejing De, Tao Tan, Jianjie Ma, Ki Bum Lee

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core-shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis.

Original languageEnglish (US)
Pages (from-to)9379-9387
Number of pages9
JournalACS Nano
Volume8
Issue number9
DOIs
StatePublished - Sep 23 2014

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Keywords

  • amphipathic tail-anchoring peptide
  • combined therapy
  • magnetic core-shell nanoparticle
  • magnetic hyperthermia
  • magnetically facilitated delivery
  • mitochondria-targeting peptide

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