ONOO- generator constructed by a small molecule photosensitizer and photoinduced NO donor for tumor therapy

Abstract

Multimodal synergistic therapy is an effective means to improve the therapeutic effects of cancer. Herein, a nanotherapeutic platform for highly efficient photodynamic and NO synergistic therapy through the generation of peroxynitrite (ONOO-) was constructed. Specifically, a new small molecule photosensitizer (DMATPE-MN) and photoinduced NO donor (NTA-CN) were subtly designed, which displayed the similar light absorption in visible light region. Under the same light irradiation, DMATPE-MN and NTA-CN can generate superoxide anion free radical (O2.-) and NO radical, respectively. Then, NTA-CN and DMATPE-MN were respectively integrated together into the nanocarriers formed by amphiphilic pillararene (WP5-PEG-OH) through host-guest and hydrophilic/hydrophobic mechanisms. Exhilaratingly, the NO generation efficiency of NTA-CN can be significantly improved after host-guest complexed with WP5-PEG-OH. The more exciting thing is that the formed nanodrugs WP5-NTA/MN can generate ONOO- after light irradiation. As a result, WP5-NTA/MN exhibited outstanding biocompability, and showed high tumor cell lethality both under the normoxic and hypoxic conditions. Furthermore, the experimental results in vivo also demonstrated its good biosafety and capability to inhibit tumor growth. Therefore, we provided a highly promising nanoplatform for multimodal synergistic therapy.