NIR-II Dye-Based Multifunctional Telechelic Glycopolymers for NIR-IIa Fluorescence Imaging-Guided Stimuli-Responsive Chemo-Photothermal Combination Therapy

Optical imaging-guided chemo-photothermal combination therapy of cancers has attracted considerable attention, because of its capacity for personalized, precision treatment and its synergistic chemo-photothermal therapeutic effect. However, it still encounters many barriers, including an unsatisfactory diagnostic accuracy, poor physiological stability, low drug loading, and uncontrolled drug release. Here, we developed a NIR-II dye-based multifunctional telechelic glycopolymer (TTQ-TC-PFru) as a drug carrier and constructed stimuli-responsive PFru-BTZ-PBOB nanoparticles (NPs) to achieve the near-infrared IIa (NIR-IIa, 1300-1400 nm) fluorescence imaging (FI)-guided chemo-photothermal combination therapy of cancers. This multifunctional glycopolymer not only serves as the contrast agent for NIR-IIa FI but also functions as the photothermal agent for photothermal therapy (PTT). Meanwhile, the fructose polymer on TTQ-TC-PFru forms a stable boronic acid-catechol conjugate with the dipeptidyl boronic acid proteasome inhibitor bortezomib (BTZ) to achieve high drug loading (31%), satisfactory physiological stability, and controlled drug release in the acidic tumor microenvironment. In addition, one BOB-containing copolymer POEGMA-co-PBOB was introduced to further improve the stability of the system. In living tumor-bearing mice, the successfully constructed stimuli-responsive NPs PFru-BTZ-PBOB induced significant tumor regression through NIR-IIa FI-guided chemo-photothermal combination therapy. Our study thus describes the great potential of NIR-IIa FI-guided chemo-photothermal combination therapy of cancers.