Building multipurpose nano-toolkit by rationally decorating NIR-II fluorophore to meet the needs of tumor diagnosis and treatment

Phototheranostics have attracted tremendous attention in cancer diagnosis and treatment because of the noninvasiveness and promising effectiveness. Developing advanced phototheranostic agents with long emission wavelength, excellent biocompatibility, great tumor-targeting capability, and efficient therapeutic effect is highly desirable. However, the mutual constraint between imaging and therapeutic functions usually hinders their wide applications in biomedical field. To balance this contradiction, we herein rationally designed and synthesized three novel tumor-targeted NIR-II probes (QR-2PEG₃₂₁, QR-2PEG₁₀₀₀, and QR-2PEG₅₀₀₀) by conjugating three different chain lengths of PEG onto an integrin α_vβ₃-targeted NIR-II heptamethine cyanine fluorophore, respectively. In virtue of the essential amphiphilic characteristics of PEG polymers, these probes display various degree of aggregation in aqueous buffer accompanying with differential NIR-II imaging and photothermal (PTT) therapeutic performance. Both in vitro and in vivo results have demonstrated that probe QR-2PEG₅₀₀₀ has the best NIR-II imaging performance with prominent renal clearance, whereas QR-2PEG₃₂₁ possesses excellent photoacoustic signal as well as PTT effect, which undoubtedly provides a promising toolbox for tumor diagnosis and therapy. We thus envision that these synthesized probes have great potential to be explored as a toolkit for precise diagnosis and treatment of malignant tumors.