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Biomaterials. 2017 Nov;144:188-198. doi: 10.1016/j.biomaterials.2017.08.032. Epub 2017 Aug 18.

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

Author information

1
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, PR China.
2
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, PR China. Electronic address: chuanzhang@sjtu.edu.cn.
3
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, PR China. Electronic address: xyzhu@sjtu.edu.cn.

Abstract

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.

KEYWORDS:

Angiogenic vessel-targeting; Drug delivery; Hypoxia; Photodynamic therapy; Vascular endothelial growth factor

[Indexed for MEDLINE]

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