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Theranostics 2019; 9(8):2158-2166. doi:10.7150/thno.30886 This issue Cite

Research Paper

NF-κB hijacking theranostic Pt(ll) complex in cancer therapy

Yingzhong Zhu^1‡, Mingzhu Zhang^1‡, Lei Luo³, Martin R Gill⁴, Cesare De Pace⁵, Giuseppe Battaglia⁵, Qiong Zhang¹, Hongping Zhou¹, Jieying Wu¹, Yupeng Tian^1✉, Xiaohe Tian^1,2,5✉

1. Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, Anhui University, Hefei 230601, P. R. China.
2. School of Life Science. Anhui University, Hefei 230039, P. R. China.
3. College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China
4. CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK
5. Department of Chemistry, University College London, London, WC1H 0AJ, UK.
‡These authors contributed equally.

✉ Corresponding authors: yptianedu.cn; and xiaohe.tedu.cn

Abstract

Platinum complexes have been used for anti-cancer propose for decades, however, their high side effects resulting from damage to healthy cells cannot be neglected and prevent further clinical utilisation. Here, we designed a cyclometalated platinum (II) complex that can bind the endogenous nuclear factor-κB (NF-κB) protein. Employing detailed colocalization studies in co-culture cell line models, we show that by binding to NF-κB, the platinum (II) complex is capable of upregulated nuclear translocation specifically in cancer but not normal cells, thereby impairing cancer proliferation without disturbing healthy cells. In a murine tumour model, the platinum (II) complex prevents tumour growth to a greater extent than cisplatin and with considerably lower side-effects and kidney damage. Considering its weak damage to normal cells combined with high toxicity to cancer cells, this NF-κB-binding platinum complex is a potential anti-cancer candidate and acts to verify the strategy of hijacking endogenous trans-nuclear proteins to achieve cancer-cell specificity and enhance therapeutic indices.

Keywords: Theranostic, Platinum complex, Nuclear factor kappa B, Cancer therapy

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