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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Immune enhancement of rhamnolipid/manganese calcium phosphate mineralized nanoparticle: A promising subunit antigen delivery system

Zheng Jia,Xinyao Zhou,Jingjing Liu,Xinqi De,Yifan Li,Zaixing Yang,Haoyuan Duan,Fang Wang,Junwei Ge

The use of biomimetic mineralization strategy is promising to solve the problem of poor stability and immune effect of subunit antigens. However, non-specifically inducing protein mineralization is still a challenge. we hypothesized that rhamnolipids with both protein and metal binding capacity could be used to develop more functional and biocompatible calcium mineralized nanoparticle (RMCP). The results show that rhamnolipids synergistically enhanced the mineralization of protein with manganese ions and improved 21 % the loading antigens of RMCP compared to manganese calcium phosphate nanoparticles. Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS) showed particle size of RMCP is 260 ± 12.1 nm with spherical morphology. In vitro experiments have shown that RMCP effectively activate immune cells through the cGAS-STING and NLRP3 pathways and demonstrated a higher level of cytokines in RAW264.7 Macrophages. In vivo, RMCP triggered an increased IgG titer with 16.5-fold IgG2a/IgG1 ratio compared to the aluminum adjuvant which improved the recovery status after challenge in mice. We used biological surfactants for the first time to enhance the biomimetic mineralization process of subunit antigen, which provides a new approach for constructing calcium-based biocompatible antigen delivery vectors, helping to develop a new generation of stable, efficient, and safe subunit vaccines.

CAS / MDL: 10043-52-4 7785-87-7
研究领域: 免疫学 · 纳米技术 · 疫苗开发 · 生物材料
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Asian Journal of Pharmaceutical Sciences · 2022 · IF 9.273

Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors

Xudong Fan,Tianxiang Yue,Aidi Liu,Xiaowei Xie,Weixiang Fang,Yinghui Wei,Hangsheng Zheng,Hongyue Zheng,Meiqi Zhou,Jigang Piao,Fanzhu Li

Photothermal therapy (PTT) has brought hope for cancer treatments, with hyperthermia-induced immunogenic cell death (ICD), which is a critical part of therapeutically induced antitumor immune responses. Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation, therefore demonstrating urgent requirements for ICD amplifier. Herein, a sub-10 nm supramolecular nanoassembly was formed by co-assembly of clinically approved aluminum adjuvant and commonly used indocyanine green (ICG) under the assistance of lignosulfonate (LS, a green and sustainable multifunctional lignin derivative) for localized photothermal-immunotherapy of breast cancer. The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD, efficiently eliciting solid immune responses through dendritic cells (DCs) activation and cytotoxic T-cell responses initiation for tumor killing. Moreover, anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity. The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy, which shows promise for delivering other therapeutics in biomedical applications.

CAS / MDL: 7446-70-0 3599-32-4
研究领域: 癌症治疗 · 纳米技术 · 免疫疗法 · 生物医学工程 · 药学
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Biomaterials Science · 2024 · IF 5.8

Preparation of Viromimetic Rod-Like Nanoparticle Vaccine (RLNVax) and Study of Their Humoral Immune Activation Efficacy

Zichao Huang,Zhenyi Zhu,Liping Liu,Wantong Song,Xuesi Chen

Virus-like nanoparticle vaccines can efficiently activate the humoral immune response by cross-linking B cell receptors with their surface multivalent antigen arrays. This structurally dependent mechanism makes it crucial to regulate and optimize structural parameters to enhance the efficacy of nanoparticle vaccines. In this study, we prepared nanoparticle vaccines with different aspect ratios by chemically modifying antigen proteins onto the surfaces of poly(amino acid) nanoparticles of various shapes (spherical, ellipsoidal, and rod-like). This allowed us to investigate the impact of structural anisotropy on the humoral immune activation efficacy of nanoparticle vaccines. Furthermore, the end-group molecules of poly(amino acid) materials possess aggregation-induced emission (AIE) properties, which facilitate monitoring the dynamics of nano-assemblies within the body. Results showed that rod-like nanoparticle vaccine (RLNVax) with higher aspect ratio (AR=5) exhibited greater lymph node draining efficiency and could elicit more effective B cell activation compared to conventional isotropic spherical nanoparticle vaccine. In a murine subcutaneous immunization model using ovalbumin (OVA) as a model antigen, RLNVax elicited antigen-specific antibody titers that were about 64 times and 4.6 times higher than those induced by free antigen protein and spherical nanoparticle vaccine, respectively. Additionally, when combined with aluminum adjuvant, antibody titers elicited by RLNVax were further enhanced by 4-fold. These findings indicate that the anisotropic rod-like structure is advantageous for improving the humoral immune activation efficacy of nanoparticle vaccines, providing significant insights for the design and optimization of next-generation nanoparticle vaccines.

研究领域: 纳米技术 · 免疫学 · 疫苗开发 · 生物医学工程
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Fundamental Research · 2023 · IF 6.2

Mannan-decorated STING-activating vaccine carrier for spatial coordinative stimulating antigen-specific immune responses

Liping Liu,Jiayu Zhao,Zichao Huang,Yudi Xu,Hongyu Chen,Ruirui Qiao,Wantong Song,Zhaohui Tang,Thomas P. Davis,Xuesi Chen

ABSTRACT In recent years, the use of nanotechnologies to improve immunotherapy efficiency has attracted increasing interest in preventive and therapeutic cancer vaccine design. However, current nanocarriers are restricted by difficulties in the systematic spatial coordinative transport of antigens, which greatly hampers the immune response efficacy of nanovaccines. Herein, we designed a mannan-decorated stimulator of the interferon genes (STING)-activating vaccine carrier for spatial coordinative stimulation of antigen-specific immune responses and elicitation of robust antitumor immunity. Mannan-decoration as the shell could significantly enhance the lymph node draining ability of the nanovaccines, especially in CD8 + dendritic cells (DCs). Azole molecule end-capped polylactic acid-polyethylenimine (PLA-PEI-4BImi) with innate stimulating activity was applied as the inner core for coordinating antigen-presenting cell (APC) activation and antigen cross-presentation. In the in vivo therapy study, single usage of this nanovaccine could achieve a 93% tumor suppression rate in the B16-OVA tumor model, which is superior to the commercialized aluminum adjuvant. This study demonstrates that a rational design of vaccine carriers for solving spatial transmission issues could greatly improve cancer vaccine efficiencies.

研究领域: 纳米技术 · 免疫学 · 癌症研究 · 生物医学工程 · 药学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

A xanthan gum and carbomer-codispersed divalent manganese ion-loaded tannic acid nanoparticle adjuvanted inactivated pseudorabies virus vaccine induces balanced humoral and cellular immune responses

Anan Guo,Lvqing Tang,Bing Yang,Niling Xie,Yandong Cui,Wen Sun,Yuan Li,Xiangting Li,Yang Wu,Yingshuai Liu

Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn 2+ ) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn 2+ -loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn 2+ -loaded nanoadjuvant for veterinary vaccines.

研究领域: 兽医学 · 免疫学 · 纳米技术 · 病毒学
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