2. Academic Validation
  3. Sonodynamic and sonomechanical effect on cellular stemness and extracellular physicochemical environment to potentiate chemotherapy

Sonodynamic and sonomechanical effect on cellular stemness and extracellular physicochemical environment to potentiate chemotherapy

  • J Nanobiotechnology. 2024 Jun 21;22(1):358. doi: 10.1186/s12951-024-02623-0.
Danli Sheng 1 2,  Tianzhi Liu 3 4,  Lang Qian 1 2,  Jufeng Chen 5,  Yi Wei 1 2,  Hangrong Chen 6,  Cai Chang 7 8
Affiliations

Affiliations

  • 1 Department of Medical Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
  • 3 State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China. ltzamazing@163.com.
  • 4 School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. ltzamazing@163.com.
  • 5 State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China.
  • 6 State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China. hrchen@mail.sic.ac.cn.
  • 7 Department of Medical Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China. changc61@163.com.
  • 8 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. changc61@163.com.
PMID: 38907270 DOI: 10.1186/s12951-024-02623-0
Abstract

Background: Hypoxia-activated prodrug (HAP) is a promising candidate for highly tumor-specific chemotherapy. However, the oxygenation heterogeneity and dense extracellular matrix (ECM) of tumor, as well as the potential resistance to chemotherapy, have severely impeded the resulting overall efficacy of HAP.

Results: A HAP potentiating strategy is proposed based on ultrasound responsive nanodroplets (PTP@PLGA), which is composed of protoporphyrin (PpIX), perfluoropropane (PFP) and a typical HAP, tirapazamine (TPZ). The intense vaporization of PFP upon ultrasound irradiation can magnify the sonomechanical effect, which loosens the ECM to promote the penetration of TPZ into the deep hypoxic region. Meanwhile, the PpIX enabled sonodynamic effect can further reduce the oxygen level, thus activating the TPZ in the relatively normoxic region as well. Surprisingly, abovementioned ultrasound effect also results in the downregulation of the stemness of Cancer cells, which is highly associated with drug-refractoriness.

Conclusions: This work manifests an ideal example of ultrasound-based nanotechnology for potentiating HAP and also reveals the potential acoustic effect of intervening Cancer stem-like cells.

Keywords

Cancer stem-like cell; Deep penetration; Nanodroplet; Tumor hypoxia; Ultrasound.

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