Citation: Kun Shang, Yinghua Lv, Yibo Yang, Senyu Yang, Zelong Chen, Ke Yang, Cong Li, Shuang Chao, Yuchao Lu, Yuxin Pei, Zhichao Pei. "Dual sweet" supramolecular glycosyl-nanoproteins based on carbohydrate-protein interaction for targeted drug delivery in vivo[J]. Chinese Chemical Letters, ;2026, 37(7): 111798. doi: 10.1016/j.cclet.2025.111798 shu

"Dual sweet" supramolecular glycosyl-nanoproteins based on carbohydrate-protein interaction for targeted drug delivery in vivo

Kun Shang ^{a, c, 1} ,
Yinghua Lv ^{a, 1} ,
Yibo Yang ^{a, 1} ,
Senyu Yang ^a ,
Zelong Chen ^a ,
Ke Yang ^a ,
Cong Li ^a ,
Shuang Chao ^{a, *,} ,
Yuchao Lu ^{b, *,} ,
Yuxin Pei ^{a, *,} ,
Zhichao Pei ^{a, *,}

a.
College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China
b.
School of Pharmacy, Changzhi Medical College, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, Changzhi 046000, China
c.
Yan'an Medical College of Yan'an University, Yan'an 716000, China

chaoshuang@nwafu.edu.cn

luyuchao@czmc.edu.cn

peiyx@nwafu.edu.cn

peizc@nwafu.edu.cn

Received Date: 24 March 2025
Revised Date: 25 August 2025
Accepted Date: 7 September 2025
Available Online: 9 September 2025

Figures(8)

Biomolecular self-assembly systems form the cornerstone of biological structures, in which the interactions between carbohydrates and proteins play a crucial role in many life processes. This has driven the development of biomimetic carbohydrate-protein supramolecular assemblies (BCPSAs), which show great potential in biomedical research. We successfully constructed a novel supramolecular hybrid nanocarrier with pH responsiveness and targeting capabilities based on specific interactions between carbohydrates and proteins. This system self-assembles into nanoparticles CA@MP5 in water through the specific binding of mannose clusters on glycosylated pillar[5]arene MP5 with lectin Con A. Additionally, through a host-guest assembly strategy with the synthesized β-d-galactopyranosyl pyridine derivative G, it complexes within the MP5 cavity to form a "double-sweet" supramolecular glyco-nanoprotein (CA@MP5⊃G). This system shows high affinity for the asialoglycoprotein receptor (ASGPR) on HepG2 liver cancer cells. In vitro, the doxorubicin (DOX)-loaded micelles (DCA@MP5⊃G) release drug effectively in acidic environments and significantly inhibit HepG2 cell growth, with reduced toxicity toward normal cells. In vivo, the nanocarrier targets tumors effectively, reducing systemic toxicity and inhibiting tumor growth. This study offers a novel construction strategy for drug delivery systems based on carbohydrate-protein interactions in anti-tumor applications, which is significant for enhancing therapeutic efficacy.
- Carbohydrate-protein interactions,
- Glycosyl-nanoproteins,
- Supramolecular self-assembly,
- Drug-targeted delivery,
- Chemotherapy
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