Robust Anticancer Efficacy of a Biologically Synthesized Tumor Acidity-Responsive and Autophagy-Inducing Functional Beclin 1

Guo Bin Ding, Junqing Sun, Gengfeng Wu, Binchun Li, Peng Yang, Zhuoyu Li, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

As a potent autophagy inducer, Beclin 1 is essential for the initiation of autophagic cell death, and triggering extensive autophagy by targeted delivery of Beclin 1 to tumors has enormous potential to inhibit tumor growth. Yet, the therapeutic application of Beclin 1 is hampered by its inability to internalize into cells and nonselective biodistribution in vivo. To tackle this challenge, we employed a novel Beclin 1 delivery manner by constructing a functional protein (Trx-pHLIP-Beclin 1, TpB) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP), and an evolutionarily conserved motif of Beclin 1. This protein could effectively transport Beclin 1 to breast and ovarian cancer cell lines under weakly acidic conditions (pH 6.5), markedly inhibit tumor cell growth and proliferation, and induce obvious autophagy. Furthermore, the in vivo antitumor efficacy of the functional Beclin 1 against an SKOV3 xenograft tumor mouse model was tested via intravenous injection. TpB preferentially accumulated in tumors and exhibited a significantly higher tumor growth inhibition than the nontargeted Beclin 1 control, whereas no overt side effects were observed. Taken together, this study sheds light on the potential application of TpB as a highly efficient yet safe antitumor agent for cancer treatment.

Original languageEnglish (US)
Pages (from-to)5227-5239
Number of pages13
JournalACS Applied Materials and Interfaces
Volume10
Issue number6
DOIs
StatePublished - Feb 14 2018

Keywords

  • anticancer efficacy
  • autophagy induction
  • biological synthesis
  • functional Beclin 1
  • pHLIP

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint

Dive into the research topics of 'Robust Anticancer Efficacy of a Biologically Synthesized Tumor Acidity-Responsive and Autophagy-Inducing Functional Beclin 1'. Together they form a unique fingerprint.

Cite this