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An Oxygen Self-Sufficient Core-Shell Metal-Organic Framework-Based Smart Nanoplatform for Enhanced Synergistic Chemotherapy and Photodynamic Therapy.

Shen-Zhen Ren,Bin Wang,Xiao-Hua Zhu,Dan Zhu,Meilin Liu,Shu-Kai Li,Yushun Yang,Zhong-Chang Wang,Hailiang Zhu

Published 2020 in ACS Applied Materials and Interfaces

ABSTRACT

The abnormal angiogenesis and insufficient oxygen supply in solid tumor lead to intratumoral hypoxia, which severely limit the efficacy of traditional photodynamic therapy (PDT). Here, a multifunctional nanoplatform (ZDZP@PP) based on a zeolitic imidazolate framework-67 (ZIF-67) core as hydrogen peroxide catalyst, a zeolitic imidazolate framework-8 (ZIF-8) shell with pH responsive property and a polydopamine-PEG (PDA-PEG) layer for improving the biocompatibility is fabricated for not only relieving tumor hypoxia, but also enhancing the combination chemo-photodynamic therapy efficacy. The chemotherapy drug doxorubicin (DOX) and photosensitizer protoporphyrin IX (PpIX) are encapsulated in different layers independently, thus a unique two-stage stepwise release become possible. Moreover, the nanoplatform can effectively decompose hydrogen peroxide to produce oxygen and thus relieve tumor hypoxia, which further facilitate the production of cytotoxic reactive oxygen species (ROS) by PpIX under laser irradiation. Both in vitro and in vivo experiment results confirm that the combination chemo-photodynamic therapy of ZDZP@PP nanoplatform can provide more effective cancer treatment than chemotherapy or PDT alone. Consequently, the oxygen self-sufficient multifunctional nanoplatform hold promising potential to overcome hypoxia and treat solid tumors in future.

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