Prodrug-embedded angiogenic vessel-targeting nanoparticle: A positive feedback amplifier in hypoxia-induced chemo-photo therapy

Publication date: November 2017
Source:Biomaterials, Volume 144
Author(s): Dongbo Guo, Shuting Xu, Nan Wang, Huangyong Jiang, Yu Huang, Xin Jin, Bai Xue, Chuan Zhang, Xinyuan Zhu
Photodynamic therapy (PDT) induced hypoxia can significantly upregulate the expression of vascular endothelial growth factor (VEGF) at the tumor-stromal interface, resulting in a promoted angiogenesis. Thus, an angiogenesis vessel-targeting nanoparticle (AVT-NP) consisting of photosensitizer, angiogenic vessel-targeting peptide, and bioreductive prodrug is developed for a chemo-photo synergistic cancer therapy, with which anti-cancer effect is achieved first by PDT and immediately followed with hypoxia-activated cytotoxic free radicals. With targeting capability, the AVT-NPs can effectively accumulate at the tumor site due to the promoted angiogenesis in response to PDT-induced hypoxia. The more nanoparticles delivered to the tumor tissue, the higher efficacy of PDT can be achieved, resulting in a more severe hypoxia and increased angiogenesis. Therefore, the prodrug embedded AVT-NP functions as a positive feedback amplifier in the combinational chemo-photo treatment and indeed achieves an enhanced anti-tumor effect in both in vitro and in vivo studies.

Graphical abstract

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