当前位置：
X-MOL 学术
›
J. Control. Release
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Risedronate-functionalized manganese-hydroxyapatite amorphous particles: A potent adjuvant for subunit vaccines and cancer immunotherapy
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-01-23 , DOI: 10.1016/j.jconrel.2024.01.033 Xiuli Zhang 1 , Mingjing Wei 1 , Zhigang Zhang 1 , Yarong Zeng 1 , Feihong Zou 1 , Sibo Zhang 1 , Zhiping Wang 1 , Fentian Chen 1 , Hualong Xiong 1 , Yufang Li 1 , Lizhi Zhou 1 , Tingting Li 1 , Qingbing Zheng 1 , Hai Yu 1 , Jun Zhang 1 , Ying Gu 1 , Qinjian Zhao 2 , Shaowei Li 1 , Ningshao Xia 1
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-01-23 , DOI: 10.1016/j.jconrel.2024.01.033 Xiuli Zhang 1 , Mingjing Wei 1 , Zhigang Zhang 1 , Yarong Zeng 1 , Feihong Zou 1 , Sibo Zhang 1 , Zhiping Wang 1 , Fentian Chen 1 , Hualong Xiong 1 , Yufang Li 1 , Lizhi Zhou 1 , Tingting Li 1 , Qingbing Zheng 1 , Hai Yu 1 , Jun Zhang 1 , Ying Gu 1 , Qinjian Zhao 2 , Shaowei Li 1 , Ningshao Xia 1
Affiliation
|
The cGAS-STING pathway and the Mevalonate Pathway are druggable targets for vaccine adjuvant discovery. Manganese (Mn) and bisphosphonates are known to exert adjuvant effects by targeting these two pathways, respectively. This study found the synergistic potential of the two pathways in enhancing immune response. Risedronate (Ris) significantly amplified the Mn adjuvant early antibody response by 166-fold and fortified its cellular immunity. However, direct combination of Mn and Ris resulted in increased adjuvant toxicity (40% mouse mortality). By the combination of doping property of hydroxyapatite (HA) and its high affinity for Ris, we designed Ris-functionalized Mn-HA micro-nanoparticles as an organic-inorganic hybrid adjuvant, named MnHARis. MnHARis alleviated adjuvant toxicity (100% 60% survival rate) and exhibited good long-term stability. When formulated with the varicella-zoster virus glycoprotein E (gE) antigen, MnHARis triggered a 274.3-fold increase in IgG titers and a 61.3-fold surge in neutralization titers while maintaining a better long-term humoral immunity compared to the aluminum adjuvant. Its efficacy spanned other antigens, including ovalbumin, HPV18 VLP, and SARS-CoV-2 spike protein. Notably, the cellular immunity elicited by the group of gE + MnHARis was comparable to the renowned Shingrix®. Moreover, intratumoral co-administration with an anti-trophoblast cell surface antigen 2 nanobody revealed synergistic antitumor capabilities. These findings underscore the potential of MnHARis as a potent adjuvant for augmenting vaccine immune responses and improving cancer immunotherapy outcomes.
中文翻译：
利塞膦酸盐功能化锰羟基磷灰石无定形颗粒：亚单位疫苗和癌症免疫治疗的有效佐剂
cGAS-STING 途径和甲羟戊酸途径是疫苗佐剂发现的可成药靶点。已知锰 (Mn) 和双膦酸盐分别通过针对这两种途径发挥佐剂作用。这项研究发现了这两种途径在增强免疫反应方面的协同潜力。利塞膦酸盐 (Ris) 将 Mn 佐剂早期抗体反应显着放大 166 倍，并增强其细胞免疫。然而，Mn 和 Ris 的直接组合会导致佐剂毒性增加（小鼠死亡率为 40%）。结合羟基磷灰石（HA）的掺杂特性及其对Ris的高亲和力，我们设计了Ris功能化的Mn-HA微纳米颗粒作为有机-无机杂化佐剂，命名为MnHARis。 MnHARis 减轻了佐剂毒性（100% 60% 存活率）并表现出良好的长期稳定性。当与水痘带状疱疹病毒糖蛋白 E (gE) 抗原配制时，与铝佐剂相比，MnHARis 引发 IgG 滴度增加 274.3 倍，中和滴度激增 61.3 倍，同时保持更好的长期体液免疫。其功效涵盖其他抗原，包括卵清蛋白、HPV18 VLP 和 SARS-CoV-2 刺突蛋白。值得注意的是，gE + MnHARis 组引发的细胞免疫与著名的 Shingrix® 相当。此外，与抗滋养层细胞表面抗原2纳米抗体的瘤内联合给药显示出协同抗肿瘤能力。这些发现强调了 MnHARis 作为增强疫苗免疫反应和改善癌症免疫治疗结果的有效佐剂的潜力。
更新日期：2024-01-23
中文翻译：
利塞膦酸盐功能化锰羟基磷灰石无定形颗粒：亚单位疫苗和癌症免疫治疗的有效佐剂
cGAS-STING 途径和甲羟戊酸途径是疫苗佐剂发现的可成药靶点。已知锰 (Mn) 和双膦酸盐分别通过针对这两种途径发挥佐剂作用。这项研究发现了这两种途径在增强免疫反应方面的协同潜力。利塞膦酸盐 (Ris) 将 Mn 佐剂早期抗体反应显着放大 166 倍，并增强其细胞免疫。然而，Mn 和 Ris 的直接组合会导致佐剂毒性增加（小鼠死亡率为 40%）。结合羟基磷灰石（HA）的掺杂特性及其对Ris的高亲和力，我们设计了Ris功能化的Mn-HA微纳米颗粒作为有机-无机杂化佐剂，命名为MnHARis。 MnHARis 减轻了佐剂毒性（100% 60% 存活率）并表现出良好的长期稳定性。当与水痘带状疱疹病毒糖蛋白 E (gE) 抗原配制时，与铝佐剂相比，MnHARis 引发 IgG 滴度增加 274.3 倍，中和滴度激增 61.3 倍，同时保持更好的长期体液免疫。其功效涵盖其他抗原，包括卵清蛋白、HPV18 VLP 和 SARS-CoV-2 刺突蛋白。值得注意的是，gE + MnHARis 组引发的细胞免疫与著名的 Shingrix® 相当。此外，与抗滋养层细胞表面抗原2纳米抗体的瘤内联合给药显示出协同抗肿瘤能力。这些发现强调了 MnHARis 作为增强疫苗免疫反应和改善癌症免疫治疗结果的有效佐剂的潜力。
京公网安备 11010802027423号