Department of Materials Science and Engineering, United States.
Department of Materials Science and Engineering, United States; Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, United States.
Biomaterials. 2019 Oct;218:119305. doi: 10.1016/j.biomaterials.2019.119305. Epub 2019 Jun 25.
We developed glycopolyesters (GPs) via azido-sugar initiated ring-opening polymerization of O-carboxyanhydrides (OCAs) and achieved efficient in vivo cancer targeting via GP-nanoparticle (GP-NP) mediated metabolic cell labeling followed by Click reaction. GP-NP shows controlled release of azido-sugars and can efficiently label LS174T colon cancer cells with azido groups in tumor-bearing mice. The exogenously introduced azido groups render excellent in vivo cancer targeting and retention of dibenzocyclooctyne-Cy5 (DBCO-Cy5) with an increasing tumor retention enhancement over time (68% at 6 h, 105% at 24 h, and 191% at 48 h) compared to control mice without azido labeling. The tumor accumulation of DBCO-doxorubicin is also significantly enhanced in GP-NP pretreated mice, resulting in improved in vivo anticancer efficacy. This study, for the first time, proposes the use of azido-sugar initiated polymerization of OCAs to form sugar delivery vehicles with high stability and controlled release, and demonstrates the increasing tumor targeting effect of DBCO-cargo over time by azido-modified tumor cells.
我们通过叠氮糖引发的 O-羧基酸酐（OCAs）开环聚合合成了糖基聚酯（GPs），并通过 GP-纳米粒子（GP-NP）介导的代谢细胞标记和随后的点击反应实现了高效的体内癌症靶向。GP-NP 显示出叠氮糖的控制释放，并能有效地用叠氮基团标记荷瘤小鼠中的 LS174T 结肠癌细胞。外源性引入的叠氮基团赋予了出色的体内癌症靶向和保留 dibenzocyclooctyne-Cy5（DBCO-Cy5）的能力，与没有叠氮标记的对照小鼠相比，随着时间的推移，肿瘤保留增强（6h 时为 68%，24h 时为 105%，48h 时为 191%）。在 GP-NP 预处理的小鼠中，DBCO-阿霉素的肿瘤积累也显著增强，从而提高了体内抗癌疗效。本研究首次提出使用叠氮糖引发的 OCAs 聚合来形成具有高稳定性和控制释放的糖输送载体，并通过叠氮修饰的肿瘤细胞证明了 DBCO-货物的肿瘤靶向作用随时间的增加而增强。
