Depletion of collagen by losartan to improve tumor accumulation and therapeutic efficacy of photodynamic nanoplatforms

Abstract

Nanocarriers for drug delivery have made great progress in the treatment of cancer, but the dense extracellular collagen of tumors has greatly limited the efficiency of drug delivery. In this study, losartan is used to deplete tumor collagen and improve the delivery efficiency and photodynamic therapeutic efficacy of chlorine 6 (Ce6)-loaded periodic mesoporous organosilica nanoplatform (Ce6-PMO) for breast cancer. After pretreatment with losartan in vivo, the tumor collagen I fraction is significantly reduced by 53% compared to that of mice pretreated with saline. Importantly, the accumulation of the Ce6-PMO nanoplatforms in the tumor is remarkably enhanced via peritumoral and intravenous injection, respectively, after the mice are pretreated with losartan. Further, combination of losartan with the Ce6-PMO nanoplatforms shows the best therapeutic efficacy, and the suppression rate of tumor volume is measured up to 82%. Taken together, this study provides a very promising synergetic strategy to improve the tumor photodynamic treatment efficacy of nanoplatforms.

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Acknowledgements

This study received financial support from the National Key Basic Research Program of the PRC (2014CB744501 and 2014CB744504), the National Natural Science Foundation of China (81601555, 81601554, 81501537, and 8140070836).

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Correspondence to Shouju Wang or Zhaogang Teng or Guangming Lu.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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Tang, Y., Liu, Y., Wang, S. et al. Depletion of collagen by losartan to improve tumor accumulation and therapeutic efficacy of photodynamic nanoplatforms. Drug Deliv. and Transl. Res. 9, 615–624 (2019). https://doi.org/10.1007/s13346-018-00610-1

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Keywords

  • Losartan
  • Photodynamic therapy
  • Periodic mesoporous organosilica
  • Breast cancer