唾液酸功能化靶向给药系统: 与唾液酸结合免疫球蛋白样凝集素或选择素受体结合的肿瘤和炎症治疗进展

doi:10.5246/jcps.2023.10.064

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (10): 773-795.DOI: 10.5246/jcps.2023.10.064

• 【综述】 • 下一篇

唾液酸功能化靶向给药系统: 与唾液酸结合免疫球蛋白样凝集素或选择素受体结合的肿瘤和炎症治疗进展

李楷¹^,²^,^#, 唐冰洁¹^,²^,^#, 柴新龙¹^,², 平洋¹^,², 王丽红¹^,², 苏瑾¹^,²^,^*()

1. 佳木斯大学药学院, 黑龙江佳木斯 154007
2. 黑龙江省新药创制与药效毒理评价重点实验室, 黑龙江佳木斯 154007

收稿日期:2023-03-07 修回日期:2023-03-23 接受日期:2023-05-21 出版日期:2023-11-04 发布日期:2023-11-04
通讯作者: 苏瑾
作者简介:
+ Tel.: +86-13803659063, E-mail: sujin@jmsu.edu.cn
基金资助:
“Northern Medicine and functional food”, Heilongjiang “Double first-class” specialty construction project (Grant No. 2018-TSXK-02), The project for scientific research of colleges and universities of The Department of Education of Heilongjiang Province (2020-KYYWF-0248) and the Jiamusi University Science and Technology Innovation Team University-level Innovation Team (Grant No. cxtd202103).

Sialic acid-functionalized targeted drug delivery systems: advances in tumor and inflammation therapy by binding to Siglecs or selectin receptors

Kai Li¹^,²^,^#, Bingjie Tang¹^,²^,^#, Xinlong Chai¹^,², Yang Ping¹^,², Lihong Wang¹^,², Jin Su¹^,²^,^*()

1 College of Pharmacy, Jiamusi University, Jiamusi 154007, Heilongjiang, China
2 Heilongjiang Provincial Key Laboratory of New Drug Development and Pharmacotoxicological Evaluation, Jiamusi 154007, Heilongjiang, China

Received:2023-03-07 Revised:2023-03-23 Accepted:2023-05-21 Online:2023-11-04 Published:2023-11-04
Contact: Jin Su
About author:
# Kai Li and Bingjie Tang contributed equally to this work.

摘要/Abstract

摘要：

靶向给药系统由于能够在特定部位实现药物的靶向释放而受到研究人员的广泛青睐, 其中主动靶向给药系统被认为是最有前途的靶向给药系统。然而, 用于构建多功能药物载体靶向部分的常用纳米材料存在许多缺点, 如生物相容性低、易被单核吞噬细胞系统消除、不易修饰等, 限制了其应用。唾液酸是一种天然配体, 通常作为糖蛋白或糖脂上聚糖的末端糖存在于细胞表面。作为一种内源性物质, 它具有生物安全性高、分子结构均匀清晰、易于化学修饰等特点。唾液酸功能化的纳米颗粒可携带靶向特异性表达其受体(唾液酸结合免疫球蛋白样凝集素或选择素受体)细胞的药物用以治疗疾病。在这篇综述中, 我们介绍了目前发表的关于以唾液酸修饰的纳米粒子为基础并结合“唾液酸结合免疫球蛋白样凝集素或选择素受体”的靶向给药系统在肿瘤或炎症中治疗作用的文献, 并讨论了天然唾液酸配体的化学修饰方法, 用以提高对受体的结合亲和力和选择性。

关键词: 唾液酸, 靶向给药系统, 唾液酸结合免疫球蛋白样凝集素, 选择素, 肿瘤, 炎症, 器官损伤

Abstract:

Targeted drug delivery systems are highly desirable for their ability to release drugs specifically at targeted sites. Among these systems, active targeting is considered the most promising. However, the nanomaterials commonly used for constructing the targeting moiety of multifunctional drug delivery vehicles have several disadvantages that limit their applications, such as low biocompatibility, susceptibility to elimination by the mononuclear phagocyte system, and difficulty in modification. Sialic acid, a natural ligand, is often present as the terminal sugar of glycans on glycoproteins or glycolipids on the cell surface. As an endogenous substance, it is highly biocompatible, has a clear molecular structure, and is easy to chemically modify. Sialic acid-functionalized nanoparticles can carry drugs that target cells expressing receptors (sialic acid-binding immunoglobulin-like lectin or selectin receptors) for the treatment of diseases. In the present review, we presented current literature on sialic acid-decorated nanoparticle-based targeted drug delivery systems that bind to “sialic acid-binding immunoglobulin-like lectin or selectin receptors” for therapeutic effects in tumors or inflammation. We also discussed chemical modification strategies for natural sialic acid ligands to improve binding affinity and selectivity to receptors.

Key words: Sialic acid, Targeted drug delivery system, Sialic acid-binding immunoglobulin-like lectin, Selectin, Tumor, Inflammation, Organ damage

Supporting:

李楷, 唐冰洁, 柴新龙, 平洋, 王丽红, 苏瑾. 唾液酸功能化靶向给药系统: 与唾液酸结合免疫球蛋白样凝集素或选择素受体结合的肿瘤和炎症治疗进展[J]. 中国药学(英文版), 2023, 32(10): 773-795.

Kai Li, Bingjie Tang, Xinlong Chai, Yang Ping, Lihong Wang, Jin Su. Sialic acid-functionalized targeted drug delivery systems: advances in tumor and inflammation therapy by binding to Siglecs or selectin receptors[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(10): 773-795.

图/表 8

Figure 1. Structures of Neu, Neu5Ac, and Neu5Gc.

Figure 2. Human and murine SA-binding immunoglobulin-like lectins (Siglecs, Sig). ITIM: Immunoreceptor tyrosine-based inhibitory motifs; ITAM: Immunoreceptor tyrosine-based activation motifs.

Figure 3. PSGL-1, CD43 on circulating leukocytes interacts with P-selectin and E-selectin on the vascular endothelium of inflamed joint synovium and controls leukocyte recruitment to joints during rheumatoid arthritis. L-selectin on leukocytes also plays a role in this process by binding endothelial PNAd to the surface of chronically inflamed blood vessels. P-selectin expressed by adherent platelets promotes further adhesion of leukocytes to the synovial vascular bed.

Figure 4. DOX-SPCL not only significantly enhances the binding of liposomes to TAMs through SA ligand/receptor interaction but also effectively promotes the lysosomal escape of internalized liposomes, thereby enhancing the antitumor effect in vivo.

Figure 5. LPS-activated HUVECs can internalize more SA-PEG-DXM/DXM micelles. SA-PEG-DXM/DXM micelles significantly attenuate the expressions of Bax and Caspase-3 and enhance the expression of Bcl-2.

Figure 6. DOX-SAL is internalized into NEs, releasing the loaded DOX, which promotes NE apoptosis and leads to blocked NE migration, ultimately resulting in NE-related inflammation.

Figure 7. Overexpression of E-selectin on peritumoral inflammatory VECs increases the accumulation of SPDD micelles in tumor tissues, whereas overexpression on tumor cells increases micelle internalization.

Table 1. High-affinity SAMs of known Siglecs.

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唾液酸功能化靶向给药系统: 与唾液酸结合免疫球蛋白样凝集素或选择素受体结合的肿瘤和炎症治疗进展

Sialic acid-functionalized targeted drug delivery systems: advances in tumor and inflammation therapy by binding to Siglecs or selectin receptors

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