Citation: Qi Wei, Hua Xin, Xiaolong Wang, Changjuan Qin, Yuanzhen Su, Di Li, Jianxun Ding. Unimolecular chiral poly(amino acid)s as adjuvants of nanovaccines for augmented cancer immunotherapy[J]. Chinese Chemical Letters, ;2025, 36(11): 111477. doi: 10.1016/j.cclet.2025.111477 shu

Unimolecular chiral poly(amino acid)s as adjuvants of nanovaccines for augmented cancer immunotherapy

Qi Wei ^{a, b} ,
Hua Xin ^{a, *,} ,
Xiaolong Wang ^{b, c} ,
Changjuan Qin ^{a, b} ,
Yuanzhen Su ^{b, c} ,
Di Li ^{b, d, *,} ,
Jianxun Ding ^{b, c, *,}

a.
Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
b.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
c.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
d.
Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130061, China

xhua@jlu.edu.cn

lidi@ciac.ac.cn

jxding@ciac.ac.cn

Received Date: 18 April 2025
Revised Date: 14 June 2025
Accepted Date: 16 June 2025
Available Online: 16 June 2025

Figures(5)

Chirality is pervasive and plays a crucial role in biological processes. Although amino acids possess inherent chirality, the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored. To address this, the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential. Among the candidates, G0-P_D-Lys₅₀ emerged as the most effective adjuvant through in vitro screening. When complexed with antigen ovalbumin (OVA) to form chiral nanovaccines, G0-P_L-Lys₅₀-OVA and G0-P_D-Lys₅₀-OVA exhibited similar morphology, particle size, and zeta potential. Despite these comparable physicochemical properties, G0-P_D-Lys₅₀-OVA induced significantly stronger activation of dendritic cells (DCs). Specifically, it resulted in 1.38- and 1.34-fold increases in CD11c⁺CD80⁺ DCs and CD11c⁺SIINFEKL-H-2Kb⁺ DCs in lymph nodes, respectively. In the LLC-OVA cancer model, G0-P_D-Lys₅₀-OVA reduced tumor volume by 50% compared to its enantiomer. These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.
- Chiral poly(amino acid)s,
- Unimolecular adjuvant,
- Nanovaccine,
- Immune activation,
- Cancer immunotherapy
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