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

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
T1-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.