Molecules (Jan 2023)

A Cell-Penetrating Peptide Modified Cu<sub>2−x</sub>Se/Au Nanohybrid with Enhanced Efficacy for Combined Radio-Photothermal Therapy

  • Ruixue Ran,
  • Sinan Guo,
  • Xiaoyu Jiang,
  • Zhanyin Qian,
  • Zhaoyang Guo,
  • Yinsong Wang,
  • Mingxin Cao,
  • Xiaoying Yang

DOI
https://doi.org/10.3390/molecules28010423
Journal volume & issue
Vol. 28, no. 1
p. 423

Abstract

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Radiotherapy (RT) is one of the main clinical therapeutic strategies against cancer. Currently, multiple radiosensitizers aimed at enhancing X-ray absorption in cancer tissues have been developed, while limitations still exist for their further applications, such as poor cellular uptake, hypoxia-induced radioresistance, and unavoidable damage to adjacent normal body tissues. In order to address these problems, a cell-penetrating TAT peptide (YGRKKRRQRRRC)-modified nanohybrid was constructed by doping high-Z element Au in hollow semiconductor Cu2−xSe nanoparticles for combined RT and photothermal therapy (PTT) against breast cancer. The obtained Cu2−xSe nanoparticles possessed excellent radiosensitizing properties based on their particular band structures, and high photothermal conversion efficiency beneficial for tumor ablation and promoting RT efficacy. Further doping high-Z element Au deposited more high-energy radiation for better radiosensitizing performance. Conjugation of TAT peptides outside the constructed Cu2−xSe/Au nanoparticles facilitated their cellular uptake, thus reducing overdosage-induced side effects. This prepared multifunctional nanohybrid showed powerful suppression effects towards breast cancer, both in vitro and in vivo via integrating enhanced cell penetration and uptake, and combined RT/PTT strategies.

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