A glycopolymersome strategy for ‘drug-free’ treatment of diabetic nephropathy,Journal of Controlled Release

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A glycopolymersome strategy for ‘drug-free’ treatment of diabetic nephropathy
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-06-25 , DOI: 10.1016/j.jconrel.2024.06.049
Jiamin Zhang ₁ , Tong Wu ₂ , Chang Li ₃ , Jianzhong Du ₄

Affiliation

Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.
Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China; Department of Gynaecology and Obstetrics, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.
Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Institute for Advanced Study, Tongji University, Shanghai 200092, China.
Department of Gynaecology and Obstetrics, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China..

Diabetic nephropathy is a severe complication of diabetes. Treatment of diabetic nephropathy is an important challenge due to persistent hyperglycemia and elevated levels of reactive oxygen species (ROS) in the kidney. Herein, we designed a glycopolymersome that can treat type 2 diabetic nephropathy by effectively inhibiting hyperglycemia and ROS-associated diabetic nephropathy pathogenesis. The glycopolymersome is self-assembled from phenylboronic acid derivative-containing copolymer, poly(ethylene oxide)--poly[(aspartic acid)--glucosamine--(phenylboronic acid)--(phenylboronic acid pinacol ester)] [PEO--P(Asp--GA--PBA--PAPE)]. PBA segment can reversibly bind blood glucose or GA segment for long-term regulation of blood glucose levels; PAPE segment can scavenge excessive ROS for renoprotection. studies confirmed that the glycopolymersomes exhibit efficient blood glucose responsiveness within 2 h and satisfactory ROS-scavenging ability with 500 M HO. Moreover, the glycopolymersomes display long-acting regulation of blood glucose levels in type 2 diabetic nephropathy mice within 32 h. Dihydroethidium staining revealed that these glycopolymersomes reduced ROS to normal levels in the kidney, which led to 61.7% and 76.6% reduction in creatinine and urea levels, respectively, along with suppressing renal apoptosis, collagen accumulation, and glycogen deposition in type 2 diabetic nephropathy mice. Notably, the polypeptide-based glycopolymersome was synthesized by ring-opening polymerization (ROP) of -carboxyanhydrides (NCAs), thereby exhibiting favorable biodegradability. Overall, we proposed a new glycopolymersome strategy for ‘drug-free’ treatment of diabetic nephropathy, which could be extended to encompass the design of various multifunctional nanoparticles targeting diabetes and its associated complications.

中文翻译：

“无药”治疗糖尿病肾病的糖聚合物体策略

糖尿病肾病是糖尿病的严重并发症。由于持续的高血糖和肾脏中活性氧（ROS）水平升高，糖尿病肾病的治疗是一个重要的挑战。在此，我们设计了一种糖聚合物体，可以通过有效抑制高血糖和ROS相关的糖尿病肾病发病机制来治疗2型糖尿病肾病。糖聚合物体由含有苯基硼酸衍生物的共聚物聚（环氧乙烷）--聚[（天冬氨酸）--葡萄糖胺--（苯基硼酸）--（苯基硼酸频哪醇酯）][PEO--P]自组装而成。 (Asp--GA--PBA--PAPE)]。 PBA片段可以可逆地结合血糖或GA片段，从而长期调节血糖水平； PAPE片段可以清除过量的ROS以保护肾脏。研究证实，糖聚合物体在 2 小时内表现出高效的血糖反应性，并在 500 M H2O 下具有令人满意的 ROS 清除能力。此外，糖聚合物体在 32 小时内对 2 型糖尿病肾病小鼠的血糖水平表现出长效调节作用。二氢乙锭染色显示，这些糖聚合物体将肾脏中的 ROS 降低至正常水平，从而使 2 型糖尿病肾病小鼠的肌酐和尿素水平分别降低 61.7% 和 76.6%，同时抑制肾细胞凋亡、胶原蛋白积累和糖原沉积。值得注意的是，基于多肽的糖聚合物体是通过羧酸酐（NCAs）的开环聚合（ROP）合成的，从而表现出良好的生物降解性。总体而言，我们提出了一种新的糖聚合物体策略，用于“无药物”治疗糖尿病肾病，该策略可以扩展到涵盖针对糖尿病及其相关并发症的各种多功能纳米颗粒的设计。

更新日期：2024-06-25

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