Bright NIR-II emissive cyanine dye-loaded lipoprotein-mimicking nanoparticles for fluorescence imaging-guided and targeted NIR-II photothermal therapy of subcutaneous glioblastoma

Cyanine dye-containing nanoparticles have widely been used in "all-in-one" NIR fluorescence imaging (FI)-guided photothermal therapy (PTT) because of their intrinsically large extinction coefficient and available physical and chemical modulation methods to tune absorption and emission wavelengths. The combination of good brightness and excellent tumor-targeting capacity is the key to realize efficient NIR-II FI-guided PTT. In this study, by covalently decorating NIR-II absorptive cyanine dyes with bulky AIE motify, we demonstrate how steric hindrance suppresses π-π stacking-induced fluorescence quenching and contributes to the good brightness of NIR-II FI of subcutaneous glioblastoma. The resulting cyanine dye (C₁₂-TPAE) is 5 times brighter than the original cyanine dye in the formulated liposomal nanoparticles and C₁₂-TPAE-AL has a high photothermal conversion efficiency of 62.4%, with good colloidal and light stability. Importantly, the ApoE peptide is absorbed on the liposomal surface, yielding lipoprotein-mimicking nanoparticles, which achieve active targeting of glioblastoma and efficient FI-guided PTT without tumor recurrence without any side effects on normal organs (heart, kidneys, liver, spleen, or lung). This research highlights a facile design route for bright NIR-II emissive and NIR-II photothermal cyanine dyes and indicates that cyanine dye-containing biomimetic theranostic nanoplatforms are promising candidates for future precision therapy.