Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy

Hongfang Chen,Haohan Huang,Haijun Tian,Jinwu Wang,Yuanjing Xu,Zhiyuan Zhang,Yan Chen,Yifan Zhou,Kai Feng,Wenhao Wang,Yuanqing Mao,Xin Wang,You Fu

doi:10.1186/s12951-021-01013-0

Abstract

BackgroundHypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier.ResultsThe results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment.ConclusionsBy using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited.Graphic abstract

Highlights

The fast growth and insufficient nutrient supply of solid tumors result in tumor hypoxia [1, 2], which can promote tumor angiogenesis and metastasis [3] but can lead to therapy resistance [4, 5]
We developed a microporous MOFbased nanocarrier coated with polydopamine (PDA) and encapsulating PFA and TPZ for hypoxia-activated osteosarcoma therapy
Characterization of prepared UiO‐66 and UiO‐66/PDA X-ray diffraction (XRD) and PXRD were employed to characterize the structure of the synthesized UiO-66

Summary

Introduction

The fast growth and insufficient nutrient supply of solid tumors result in tumor hypoxia [1, 2], which can promote tumor angiogenesis and metastasis [3] but can lead to therapy resistance [4, 5]. Tirapazamine (TPZ) is a bioreductive prodrug that can be transformed into tumor-toxic benzotriazinyl (BTZ). Many studies have focused on creating a penetrable and hypoxic intratumor microenvironment to enhance the toxicity of hypoxia-sensitive prodrugs [13,14,15]. A nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier

Methods

Results

Discussion

Conclusion