NIR-II Light Excited Heptamethine Cyanine/Prodrug/Albumin Nanoparticles for Photothermal/Photodynamic/Chemo Combination Therapy

Second near-infrared (NIR-II) phototheranostics, operating in the second near-infrared region (>1000 nm), offer significant advantages for tumor diagnosis and therapy, making them highly promising in biomedical research. In this study, we successfully synthesized a heptamethine cyanine molecule fluorophore (IRCS-1060), which exhibits excitation and emission spectra in the NIR-II region. The BIT NPs (BSA@IRCS-1060@TPZ Nanoparticles) were fabricated by integrating the heptamethine cyanine molecule fluorophore (IRCS-1060) with bovine serum albumin (BSA) and the hypoxic-activated prodrug tirapazamine (TPZ). Under the irradiation of NIR laser, the BIT NPs can provide NIR-II optical imaging (fluorescence imaging (FI) and photoacoustic imaging (PAI)) guided photothermal/photodynamic (PTT/PDT) therapy. Moreover, PDT exacerbated the hypoxic environment of the tumor microenvironment, subsequently activating the TPZ and initiating a cascade chemotherapy process. The combination of NIR-II PTT/PDT and chemotherapy could effectively suppress the growth of tumors with negligible side effects. This work presents a highly promising 1064 nm laser excitation phototheranostic agent for spatiotemporally specific diagnosis and combination therapy of tumors.