A near-infrared phototheranostic probe for in vivo hyaluronidase detection and activatable imaging-guided synergistic therapy of triple negative breast cancer

Activatable phototheranostic probes may become novel option for tumor diagnosis and treatment due to their abilities to accurately detect cancer and guide therapeutic intervention through imaging. In this study, a hyaluronidase (HAase)-responsive near-infrared phototheranostic probe (HA-ICG-PDA) has been developed by covalently coating indocyanine green (ICG)-decorated hyaluronic acid (HA) onto the surface of polydopamine (PDA) for the imaging and therapy of triple negative breast cancer (TNBC). The probe exhibits sensitive and selective fluorescence enhancement to HAase, enabling the detection of HAase and activatable near-infrared fluorescence imaging of HAase-overexpressed tumor cells. Moreover, the combination of ICG and PDA equips HA-ICG-PDA with outstanding photodynamic and enhanced photothermal effects upon 808 nm laser irradiation. Both in vitro and in vivo experiments have confirmed that HA-ICG-PDA is capable of realizing imaging diagno-sis of TNBC through HAase-activated fluorescence signal. With the guidance of fluorescence imaging, the probe displays synergistic photothermal and photodynamic therapy effects against TNBC, with minimal damage to the normal tissues. Therefore, the proposed phototheranostic probe paves a new avenue for HAase detection, and subsequently, diagnosis and imaging-guided treatment of TNBC.