Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers

Giimel Ajnai, Chun Chia Cheng, Tzu Chun Kan, Jeng Wei Lu, Sri Rahayu, Amy Chiu, Jungshan Chang

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we successfully formulated and assessed the biochemical and therapeutic roles of the conjugated gold nanoparticles–Tirapazamine (GNPs–TPZ) on therapeutic assessments of MKN45-induced xenograft animal model. The results indicated that GNPs–TPZ was a potential nanomedicine for selectively targeting hypoxia tumors coupled with decreased side effects on healthy tissue or organs. TPZ significantly reduced cell viability of hypoxic gastric cancer MKN45 cells, but not in cells incubated in normoxia condition. For improving tumor targeting efficiency, furthermore, the GNPs drug carrier was conjugated to TPZ via biding mediator bovine serum albumin (BSA), and we demonstrated that this conjugated GNPs–TPZ retained the unique characteristics of hypoxic toxin and possessed the adequate feature of systemic bio-distributions in animals. GNPs–TPZ nanoparticles revealed their superior affinity to hypoxia tumors in the MKN45 xenograft. Moreover, GNPs– TPZ treatments did not significantly alter the biochemical parameters of blood samples acquired from animals. Taken together, TPZ, a prodrug activated by hypoxia, was conjugated with GNPs, whereas BSA severed as an excellent binding agent for preparing the conjugated GNPs–TPZ nanomedicines. We demonstrated that GNPs–TPZ enhanced tumor targeting, resulting in higher therapeutic efficacy compared to TPZ. We suggest that it may sever as an adjuvant treatment or combined therapy with other chemotherapeutics for the treatment of cancer patients in the future.

Original languageEnglish
Article number847
JournalPharmaceutics
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2022

Keywords

  • bovine serum albumin
  • gold nanoparticles (GNPs)
  • hypoxia
  • MKN45 cells
  • Tirapazamine (TPZ)
  • xenograft

ASJC Scopus subject areas

  • Pharmaceutical Science

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