ACS Nano
·
2025
·
IF 16
Chang Liu,Yuxi Gao,Yibo Qi,Zhenyi Zhu,Liping Liu,Kuncheng Lv,Xiaoye Lin,Yang Yu,Xinghui Si,Wantong Song,Wei Li
Exploiting localized, sustained-release drug delivery carriers to enhance the efficiency of tumor immunotherapy has become a major research interest. However, due to the multistep nature of immune activation and the need to target multiple sites─such as simultaneously activating both tumors and lymph nodes─using a single delivery carrier to meet all the complex requirements of immune activation poses significant challenges and limitations. Here, we report a self-adjuvant gel (SAG) for the delivery of the chemotherapeutic agent doxorubicin (DOX) and the immune adjuvant TLR-9 agonist CpG to tumor sites and lymph nodes, enabling sequential, multistep immune activation. This SAG is cross-linked by polyethylenimine grafted with 4-benzimidazole (PEI-4BImi), which has innate immune activation properties, with oxidized dextran. The released PEI-4BImi further assembles in situ with tumor antigens to form nanoparticles of appropriate sizes that can drain to the lymph nodes, promoting antigen presentation and dendritic cell (DC) activation. The SAG exhibits sustained degradation and drug release both in vitro and in vivo over 25 days, efficiently transporting CpG and antigens to the lymph nodes and enhancing DC activation within the lymph nodes. In vivo therapeutic results demonstrated that the SAG could suppress tumor growth, achieving 93% tumor inhibition rates in a subcutaneous liver tumor model and 97% in an orthotopic colon tumor model. Importantly, the immune activation mechanisms, including antigen release and presentation, DC activation, and T-cell priming, were further confirmed through flow cytometry, RNA-seq, and proteomics. Collectively, this SAG presents a potent targeted strategy for cancer immunotherapy.
研究领域:
肿瘤学
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免疫学
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生物材料
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药物递送
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转化医学
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分子影像
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 11
·2865-2876
·
IF 7.59
Mengyue Pei,Huiyang Li,Yingwei Zhu,Jian Lu,Chuangnian Zhang
Liver cancer is the most common malignant tumor and liver cancer immunotherapy has been one of the research hotspots. To induce antigen-specific antitumor immune responses against liver cancer, we developed antigen and adjuvant co-delivery nanovaccines (APPCs). Polyanionic alginate (ALG) and polycationic polyethyleneimine (PEI) were utilized to co-deliver a glypican-3 peptide antigen and an unmethylated cytosine-phosphate-guanine (CpG) adjuvant by electrostatic interactions. A cellular uptake study confirmed that APPC could promote antigen and adjuvant uptake by dendritic cells (DCs). Importantly, APPC facilitated the endosomal escape of the peptide for antigen delivery into the cytoplasm. In addition, APPC showed significant stimulation of DC maturation in vitro. APPC could also efficiently prime DCs and induce cytotoxic T lymphocyte responses in vivo. The in vitro cell viability assay and the in vivo histocompatibility showed that APPC was non-toxic within the tested concentration. This study demonstrates that the peptide antigen and the CpG adjuvant co-delivery nanovaccine have potential applications in liver cancer immunotherapy.
研究领域:
免疫学
·
肿瘤学
·
分子生物学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Yang Sui,Ji Li,Jiqiang Qu,Ting Fang,Hongyan Zhang,Jian Zhang,Zheran Wang,Mingyu Xia,Yinghui Dai,Dongkai Wang
Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years. A major challenge of cancer vaccine is to target cytosols of dendritic cells (DCs) in the lymph nodes (LNs) to enhance efficiency of antigen cross-presentation, which elicits high levels of cytotoxic T-lymphocytes to destruct tumor cells. Here, we address this issue by conjugating ovalbumin (OVA) to PEG-PCL using disulfide bond (-ss-), and the degradable pH-responsive polymer-PEI-PCL as delivery carrier. In addition, the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to LNs. Subsequently, CpG ODN 1826 , a TLR-9 agonist, was further introduced into a mixed micelle of 30 nm or less as a unique tumor vaccine. Importantly, the results demonstrated the mixed micelles with 1:1 mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs, meanwhile, OVA was modified to the surface of mixed micelles via disulfide bonds (-ss-) for promotion efficiency of antigen cross-presentation. More surprisingly, combination of tumor vaccine with anti-PD-1, the therapy of ectopic melanoma (B16-OVA) and lung metastasis melanoma (B16-OVA) is excellent therapeutic effect. Taken together, our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
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药物递送系统
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）