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.

中文翻译：

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基于NIR-II染料的多功能远螯含糖聚合物，用于NIR-IIa荧光成像引导的刺激-响应性化学-光热联合疗法

光学成像引导的化学热光疗法联合治疗已经引起了广泛的关注，因为它具有个性化，精确治疗的能力以及其协同的化学光热疗法的疗效。但是，它仍然遇到许多障碍，包括诊断准确性不佳，生理稳定性差，载药量低和药物释放不受控制。在这里，我们开发了一种基于NIR-II染料的多功能远螯糖聚合物（TTQ-TC-PFru）作为药物载体，并构建了刺激响应型PFru-BTZ-PBOB纳米颗粒（NPs）以实现近红外IIa（NIR-IIa ，1300-1400 nm）荧光成像（FI）指导的化学-光热联合治疗。这种多功能糖聚合物不仅可以用作NIR-IIa FI的造影剂，还可以用作光热疗法（PTT）的光热剂。同时，TTQ-TC-PFru上的果糖聚合物与二肽基硼酸蛋白酶体抑制剂硼替佐米（BTZ）形成稳定的硼酸-邻苯二酚共轭物，以实现高载药量（31％），令人满意的生理稳定性和受控的药物释放。酸性肿瘤微环境。此外，一种含BOB的共聚物POEGMA-引入了co- PBOB以进一步提高系统的稳定性。在活体荷瘤小鼠中，成功构建的刺激应答性NPs PFru-BTZ-PBOB通过NIR-IIa FI引导的化学光热联合疗法诱导了显着的肿瘤消退。因此，我们的研究描述了NIR-IIa FI指导的化学-光热联合治疗癌症的巨大潜力。