Therapeutic inhibitory RNA in head and neck cancer via functional targeted lipid nanoparticles

Liyona Kampel, Meir Goldsmith, Srinivas Ramishetti, Nuphar Veiga, Daniel Rosenblum, Anna Gutkin, Sushmita Chatterjee, Moran Penn, Galya Lerman, Dan Peer, Nidal Muhanna

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Currently there are no specific therapies addressing the distinctive biology of human papillomavirus (HPV)-induced cancer approved for clinical use. Short interfering RNA (siRNA) has much potential for therapeutic manipulation of HPV E6/E7 oncoproteins. Lipid-based nanoparticles (LNPs) can be utilized for systemic transportation and delivery of siRNA at target site. We recently developed a recombinant protein linker that enables uniform conjugation of targeting antibodies to the LNPs. Herein, we demonstrate the therapeutic efficacy of anti-E6/E7 siRNA delivered via targeted LNPs (tLNPs) in a xenograft HPV-positive tumor model. We show that anti-epidermal growth factor receptor (EGFR) antibodies, anchored to the LNPs as targeting moieties, facilitate cargo delivery but also mediate anti-tumor activity. Treatment with siE6 via tLNPs resulted in 50% greater reduction of tumor volume compared to treatment with siControl encapsulated in isoLNPs (coated with isotype control antibodies). We demonstrate superior suppression of HPV oncogenes and higher induction of apoptosis by the tLNPs both in vitro and in vivo. Altogether, the coupling of inhibitory siE6 with anti-EGFR antibodies, that further elicited anti-tumor effects, successfully restricted tumor progression. This system that combines potent siRNA and therapeutically functional tLNPs can be modulated against various cancer models.

Original languageEnglish (US)
Pages (from-to)378-389
Number of pages12
JournalJournal of Controlled Release
Volume337
DOIs
StatePublished - Sep 10 2021

Keywords

  • HPV
  • Head and neck cancer
  • Lipid-based nanoparticle
  • Targeting
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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