Journal of Nanobiotechnology (Jan 2023)

Tumor-penetrating nanoplatform with ultrasound “unlocking” for cascade synergistic therapy and visual feedback under hypoxia

  • Zhuoyan Xie,
  • Junrui Wang,
  • Yuanli Luo,
  • Bin Qiao,
  • Weixi Jiang,
  • Leilei Zhu,
  • Haitao Ran,
  • Zhigang Wang,
  • Wei Zhu,
  • Jianli Ren,
  • Zhiyi Zhou

DOI
https://doi.org/10.1186/s12951-023-01765-x
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 20

Abstract

Read online

Abstract Background Combined therapy based on the effects of cascade reactions of nanoplatforms to combat specific solid tumor microenvironments is considered a cancer treatment strategy with transformative clinical value. Unfortunately, an insufficient O2 supply and the lack of a visual indication hinder further applications of most nanoplatforms for solid tumor therapy. Results A visualizable nanoplatform of liposome nanoparticles loaded with GOD, H(Gd), and PFP and grafted with the peptide tLyP-1, named tLyP-1H(Gd)-GOD@PFP, was constructed. The double-domain peptide tLyP-1 was used to specifically target and penetrate the tumor cells; then, US imaging, starvation therapy and sonodynamic therapy (SDT) were then achieved by the ultrasound (US)-activated cavitation effect under the guidance of MR/PA imaging. GOD not only deprived the glucose for starvation therapy but also produced H2O2, which in coordination with 1O2 produced by H(Gd), enable the effects of SDT to achieve a synergistic therapeutic effect. Moreover, the synergistic therapy was enhanced by O2 from PFP and low-intensity focused ultrasound (LIFU)-accelerated redox effects of the GOD. The present study demonstrated that the nanoplatform could generate a 3.3-fold increase in ROS, produce a 1.5-fold increase in the maximum rate of redox reactions and a 2.3-fold increase in the O2 supply in vitro, and achieve significant tumor inhibition in vivo. Conclusion We present a visualizable nanoplatform with tumor-penetrating ability that can be unlocked by US to overcome the current treatment problems by improving the controllability of the O2 supply, which ultimately synergistically enhanced cascade therapy.

Keywords