Chirality of poly(γ-glutamic acid) directs calcium nanoparticle assembly and adjuvant-like immune activation

  • Acta Biomater. 2026 May:215:336-349. doi: 10.1016/j.actbio.2026.04.011.
Huizhu Tan  1 ,  Kuirong Mao  1 ,  Meiling Yu  1 ,  Dongxiao Han  1 ,  Xiandi Meng  1 ,  Mengfei Zhao  1 ,  Haorui Wang  2 ,  Yanbao Xin  1 ,  Taoran Chen  1 ,  Meng Guan  3 ,  Chunsheng Xiao  4 ,  Yong-Guang Yang  5 ,  Tianmeng Sun  6
Affiliations
  • 1. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China.
  • 2. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; International Center of Future Science, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China.
  • 3. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China.
  • 4. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China. Electronic address: [email protected].
  • 5. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; International Center of Future Science, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China. Electronic address: [email protected].
  • 6. Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China; International Center of Future Science, Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China; State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin, China. Electronic address: [email protected].
PMID: 41962731 DOI: 10.1016/j.actbio.2026.04.011
Abstract

Chirality, describing the asymmetry between an object and its mirror image, plays a crucial role in biological recognition and functional material design. Translating this concept to nanoscale systems, chiral Polymers can influence nanoparticle self-assembly and cellular interactions. Here, we synthesized three calcium carbonate nanoparticles using poly (γ-glutamic acid) (PGA) with defined l-, d-, and LD-chiral configurations (L-CaNPs, d-CaNPs, and LD-CaNPs). The resulting nanoparticles exhibited comparable surface properties but distinct morphologies and optical activities, with chirality-dependent differences in their interactions with dendritic cells (DCs). Among them, l-CaNPs most effectively promoted DC activation, as evidenced by elevated expression of costimulatory markers (CD80, CD86, and MHC-II) and enhanced calcium signaling, without inducing cytotoxicity. Furthermore, when loaded with the SARS-CoV-2 S1 Protein, l-CaNPs significantly enhanced antigen-specific antibody production in mice, demonstrating adjuvant-like immunostimulatory activity without detectable cytotoxicity. These findings demonstrate that PGA chirality dictates nanoparticle morphology and immune modulation, and that l-configured CaNPs provide a promising platform for the development of safe and effective vaccine adjuvants. STATEMENT OF SIGNIFICANCE: Chirality plays a crucial role in biological recognition and functional material design. Translating this concept to nanoscale systems, chiral Polymers can influence nanoparticle self-assembly and cellular interactions. In this study, we report a chirality-engineered calcium nanoparticle platform assembled from poly (γ-glutamic acid) with defined L/D-/LD-configurations. By systematically comparing their physicochemical and biological behaviors, we demonstrate that polymer chirality governs nanoparticle assembly, resulting in distinct morphologies that differentially regulate intracellular calcium distribution and APC activation. Among them, l-CaNPs most effectively promoted DC activation, as evidenced by elevated expression of costimulatory markersand enhanced calcium signaling. when loaded with the SARS-CoV-2 S1 Protein, l-CaNPs significantly enhanced antigen-specific antibody production. This work focuses on structure-bioactivity relationships and immune modulation driven by material chirality.

Keywords
CaCO(3) nanoparticles; Chirality; Dendritic cells; Immune activation; Poly (γ-glutamic acid).
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