PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Glycyrrhiza uralensis Polysaccharide Gold Nanoparticles as Antigen Carriers and Potential Adjuvant to DC Vaccines.
Glycyrrhiza uralensis Polysaccharide Gold Nanoparticles as Antigen Carriers and Potential Adjuvant to DC Vaccines.
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宫颈癌是全球女性第四大死因,人乳头瘤病毒(HPV)被确定为主要致病因素。本研究探讨甘草多糖金纳米颗粒(GUPS-AuNPs)的免疫刺激活性和抗原递送效率,并评估以GUPS-AuNPs作为递送系统的HPV树突状细胞(DC)疫苗的抗肿瘤疗效。
通过绿色还原法合成GUPS-AuNPs,并使用SEM、EDS、TEM、UV和FT-IR光谱等先进技术进行表征。以DCs作为主要实验模型,采用流式细胞术评估GUPS-AuNPs的免疫刺激活性和抗原递送效果。此外,建立TC-1荷瘤小鼠模型,评估GUPS-AuNPs辅助的HPV-DC疫苗的免疫刺激和抗肿瘤作用。
合成的GUPS-AuNPs粒径为120.77 ± 3.13 nm,表面电荷为-11.9 ± 2.1 mV,稳定性优良。流式细胞术分析表明,GUPS-AuNPs显著增强DC成熟并促进T细胞增殖。此外,抗原递送实验显示,GUPS-AuNPs提高了DCs的抗原捕获能力。共聚焦成像证实,GUPS-AuNPs延长了抗原的细胞内滞留时间。体内研究表明,以GUPS-AuNPs为载体的HPV-DC疫苗有效抑制肿瘤生长,提高脾脏中CD4 + T和CD8 + T细胞数量,并诱导强烈的抗原特异性免疫应答。
GUPS-AuNPs有效增强DC成熟和抗原递送,显著增强HPV疫苗触发的适应性免疫应答,从而抑制肿瘤进展。本研究将GUPS-AuNPs作为一种新型、安全、高效的抗原递送平台,在疫苗开发方面具有广阔前景。
Background : Cervical cancer is the fourth leading cause of death among women worldwide, with human papillomavirus (HPV) identified as a major contributing factor.
This study investigates the immunostimulatory activity and antigen delivery efficiency of Glycyrrhiza uralensis polysaccharide gold nanoparticles (GUPS-AuNPs) and assesses the antitumor efficacy of an HPV dendritic cell (DC) vaccine using GUPS-AuNPs as a delivery system.
Methods : GUPS-AuNPs were synthesized via a green reduction method and characterized using advanced techniques, including SEM, EDS, TEM, UV, and FT-IR spectroscopy. DCs served as the primary experimental model, with flow cytometry employed to evaluate the immunostimulatory activity and antigen delivery effectiveness of GUPS-AuNPs.
Additionally, a TC-1 tumor-bearing mouse model was established to assess the immunostimulatory and antitumor effects of the HPV-DC vaccine facilitated by GUPS-AuNPs. Results : The synthesized GUPS-AuNPs exhibited a particle size of 120. 77 ± 3. 13 nm, a surface charge of -11. 9 ± 2. 1 mV, and excellent stability. Flow cytometry analysis demonstrated that GUPS-AuNPs significantly enhanced DC maturation and promoted T cell proliferation.
Furthermore, antigen delivery experiments revealed that GUPS-AuNPs improved the antigen capture capabilities of DCs. Confocal imaging confirmed that GUPS-AuNPs extended the intracellular retention time of antigens. In vivo studies showed that the HPV-DC vaccine formulated with GUPS-AuNPs as carriers effectively suppressed tumor growth, elevated the populations of CD4 + T and CD8 + T cells in the spleen, and induced a robust antigen-specific immune response.
Conclusions : GUPS-AuNPs effectively enhance DC maturation and antigen delivery, significantly boosting the adaptive immune response triggered by HPV vaccines and leading to the inhibition of tumor progression. This research introduces GUPS-AuNPs as a novel, safe, and efficient antigen delivery platform with promising potential for vaccine development.
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