Citation: Yinghua Lv, Yuchao Lu, Chenxi Hou, Jun Li, Zelong Chen, Aihua Zhen, Jiaming Ren, Yuxin Pei, Tony D James, Lan Chen, Yanjie Jia, Danhong Shang, Pengkun He, Zhongfu Wang, Zhichao Pei. Supramolecular glycosyl-nanoproteins based on host-guest chemistry for targeted co-delivery in vivo[J]. Chinese Chemical Letters, ;2026, 37(11): 112185. doi: 10.1016/j.cclet.2025.112185 shu

Supramolecular glycosyl-nanoproteins based on host-guest chemistry for targeted co-delivery in vivo

Yinghua Lv ^{a, 1} ,
Yuchao Lu ^{b, 1,*,} ,
Chenxi Hou ^{a, 1} ,
Jun Li ^a ,
Zelong Chen ^a ,
Aihua Zhen ^c ,
Jiaming Ren ^a ,
Yuxin Pei ^{a, *,} ,
Tony D James ^d ,
Lan Chen ^e ,
Yanjie Jia ^f ,
Danhong Shang ^f ,
Pengkun He ^f ,
Zhongfu Wang ^g ,
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.
Shandong Sheelian Pharmaceutical Co., Ltd., Yuncheng 274700, China
d.
Department of Chemistry, University of Bath, Bath, BA2 7AY, United Kingdom
e.
School of Public Health, Changzhi Medical College, Changzhi 046000, China
f.
College of Science & Technology, Hebei Agricultural University, Huanghua 061100, China
g.
College of Life Science, Northwest University, Xi'an 710069, China

luyuchao@czmc.edu.cn

peiyx@nwafu.edu.cn

peizc@nwafu.edu.cn

Received Date: 21 May 2025
Revised Date: 25 November 2025
Accepted Date: 26 November 2025
Available Online: 27 November 2025

Figures(7)

Supramolecular nanoproteins based on host-guest interaction can integrate different therapeutic functions into a single nano delivery system to overcome chemoresistance in tumor therapy. In this work, the biohybrid supramolecular glycosyl-nanoproteins (Bio-WP5G-Avi) were constructed via self-assembly of biotinylated glycosyl-supramolecule complex (Bio-WP5G) with streptavidin (Avi), where Bio-WP5G has formed through host-guest interaction between biotinylated pillar[5]arene (Bio-WP5) and galactosamine derivative (G), which displays excellent GSH responsiveness, enhanced hepatoma-targetability, and efficient drug co-delivery. The host molecule Bio-WP5 contains disulfide bonds that respond to high concentrations of GSH in the tumor microenvironment, while the guest molecule G contains ammonium cations for loading of polyanionic siRNA by electrostatic interaction and galactose residues for targeting hepatoma cells by carbohydrate-lectin interactions. in vitro experiments, Bio-WP5G-Avi@DOX/siRNA not only significantly improved the transfection efficiency of siRNA and exhibited effective gene silencing ability but also enhanced the toxicity of drugs to HepG2/ADR cells. Furthermore, in vivo experiments with Bio-WP5G-Avi@DOX/siRNA using HepG2/ADR tumor-bearing nude mice model confirmed good biosafety, enrichment at tumors, and enhanced therapeutic efficacy. This work provides a unique strategy to construct a supramolecular glycosyl-nanoproteins delivery system for targeted co-delivery of drug/siRNA, which could pave a novel way for targeted and combination cancer therapy.
- Biohybrid,
- Host-guest interaction,
- Supramolecular self-assembly,
- Glycosyl-nanoproteins,
- Targeted co-delivery
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