Rational Design of a Hetero-multinuclear Gadolinium(III)–Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer
Xueyu Man, Wenjuan Li, Minghui Zhu, Shanhe Li, Gang Xu, Zhenlei Zhang, Hong Liang, Feng Yang
Abstract
For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)–Cu(II) thiosemicarbazone complex ( Gd-2Cu ) and then constructed a Gd-2Cu @AFt nanoparticle (NP) delivery system. Gd-2Cu / Gd-2Cu @AFt NPs not only had significant T 1 -weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu @AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo . Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.