ACS Nano
·
2025
·
IF 16
Chendong Yang,Entao Li,Xiaoping Guo,Wenyu Xie,Yuanzhan Wang,Xuefei Huang,Sandra Chiu,Xuanjun Wu
Over the past 3 years, SARS-CoV-2 Omicron has been circulating globally with the emergence of multiple subvariants, including BA.5, BA.5.2, XBB, XBB.1, EG.5.1, HK.3, BA.2.86, JN.1, and KP.2. To combat these Omicron subvariants, several vaccines based on receptor-binding domain (RBD) dimers have been developed; however, RBD dimer vaccines require frequent updates to cope with the emergence of new variants. In contrast, the development of a safe, effective, and broad-spectrum vaccine against multiple Omicron subvariants, including the latest JN.1 and KP.2, would be a one-size-fits-all solution. Here, we designed BA.4/5 RBD-PC7A conjugate micelles by displaying the BA.4/5 RBD in PC7A micelles. Remarkably, the micelles elicited potent neutralizing antibodies (NAbs) in rabbits, effectively neutralizing BA.5.2, XBB.1.18, and HK.3 infections. Moreover, the micelles alone were able to induce NAbs in mice against the BA.5 variant. When a cytosine-phosphate-guanine (CpG) adjuvant was added and electrostatically adsorbed to the micelles, there was a significant increase in the antibody titers of IgG1, IgG2b, and IgG2c. This enhancement facilitated the broad neutralization of various strains, including BA.5.2, XBB.1.18, HK.3, JN.1, and KP.2. Furthermore, the micelles adsorbed with CpG protected golden hamsters from infection with the BA.5.2 strain. This study presents a potent and broadly neutralizing nanovaccine that includes the BA.4/5 RBD antigen and a CpG adjuvant. It demonstrates efficacy against multiple Omicron subvariants, including BA.5, BA.5.2, XBB.1.18, HK.3, JN.1, and KP.2, highlighting its potential for clinical translation.
研究领域:
免疫学
·
病毒学
·
疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Xia Dong,Jie Liang,Afeng Yang,Zhiyong Qian,Deling Kong,Feng Lv
As synergistic photothermal immunotherapy has developed as one of the most attractive strategies for cancer therapy, it is crucial to design an effective photothermal immunotherapy system to enhance the synergistic anti-tumor effect and reveal the essential role of each treatment. In this study, we designed CpG self-crosslinked nanoparticles-loaded IR820-conjugated hydrogel with dual self-fluorescence to exert the combined photothermal-immunotherapy. IR820-hydrogel can be effective for hyperthermia to eliminate the primary tumor based on its comprehensive coverage and generated photothermal-induced tumor antigens for assisted immunotherapy. CpG self-crosslinked nanoparticles improved the immune response of adjuvant against melanoma without extra nano-carriers. The synergistic photothermal immunotherapy was achieved by the merging of CpG self-crosslinked nanoparticles and IR820-hydrogel. A possible mechanism of combined antitumor effect was further revealed by analyzing immune cells including CD8 + T cells , DCs, B cells, Treg and MDSC in tumor microenvironment . The specific antitumor immunity was provoked to remove the tumor residues and ultimately the combined treatment mode achieved more effective systemic therapeutic effect than either photothermal therapy or immunotherapy alone. Furthermore, self-fluorescent IR820-hydrogel and CpG nanoparticles exerted the imaging-guided combined photothermal-immunotherapy by the dual fluorescence imaging method without additional fluorescent labeling . This visible combined photothermal-immunotherapy offers a potential for precise cancer treatment.
研究领域:
肿瘤学
·
生物医学工程
·
免疫学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Cui Tang,Hui Wang,Lina Guo,Chan Zou,Jianming Hu,Hanyong Zhang,Wenhu Zhou,Guoping Yang
Atherosclerosis (AS) is a major contributor to cardiovascular diseases, necessitating the development of novel therapeutic strategies to alleviate plaque burden. Macrophage efferocytosis, the process by which macrophages clear apoptotic and foam cells, plays a crucial role in plaque regression. However, this process is impaired in AS lesions due to the overexpression of CD47, which produces a “do not eat me” signal. In this study, we investigated the potential of CpG, a toll-like receptor 9 agonist, to enhance macrophage efferocytosis for AS therapy. We demonstrated that CpG treatment promoted the engulfment of CD47-positive apoptotic cells and foam cells by macrophages. Mechanistically, CpG induced a metabolic shift in macrophages characterized by enhanced fatty acid oxidation and de novo lipid biosynthesis, contributing to its pro-efferocytic effect. To enable in vivo application, we conjugated CpG on silver nanoparticles (AgNPs) to form CpG-AgNPs, which could protect CpG from biological degradation, promote its cellular uptake, and release CpG in response to intracellular glutathione. Combining the intrinsic antioxidative and anti-inflammatory abilities of AgNPs, such nanomedicine displayed multifunctionalities to simultaneously promote macrophage efferocytosis and repolarization. In an ApoE–/– mouse model, intravenous administration of CpG-AgNPs effectively targeted atherosclerotic plaques and exhibited potent therapeutic efficacy with excellent biocompatibility. Our study provides valuable insights into CpG-induced macrophage efferocytosis and highlights the potential of CpG-AgNPs as a promising therapeutic strategy for AS.
研究领域:
纳米医学
·
心血管疾病
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Chen Wang,Yin Li,Xiaoxue Shen,Shiwei Xiao,Huiying Du,Qianye Zhao,Ying Wang,Qiangtao Zhang,Shuxin Wen
Background Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) exhibit poor survival due to tumor microenvironment (TME) barriers and systemic toxicity of chemo-immunotherapy associated with chemo-immunotherapy. Methods An injectable thermoresponsive hydrogel was engineered by crosslinking D-α-tocopheryl polyethylene glycol succinate (TPGS) with Na₂CO₃ (15 % w/v TPGS: 9 % w/v Na₂CO₃). This platform co-encapsulated doxorubicin-loaded nanoparticles (DOX NP) synthesized via PEI-cis-aconitic acid conjugation and CpG-loaded adjuvant nanoparticles (CpG NP) prepared through genipin-mediated PEI crosslinking. The hydrogel exhibited rapid temperature-triggered gelation, shear-thinning injectability, and a macroporous architecture that enabled dual drug retention and immune cell infiltration. Results In vitro , the hydrogel provided the sustained release of DOX NP with pH-responsive acceleration in acidic TME. In vivo , localized delivery of Gel-DOX NP-CpG NP significantly suppressed tumor growth ( p < 0.05) and enhanced cytotoxic CD8 + T-cell infiltration in TME (3.1-fold) and spleens (2.4-fold). RNA sequencing revealed 88 immune-related differentially expressed genes, including downregulated immunosuppressors and enriched cytokine pathways. Conclusion This TPGS/Na₂CO₃ hydrogel platform coordinates chemotherapy-induced immunogenic cell death (DOX NP) with CpG-driven innate immunity, overcoming TME barriers to enhance localized and systemic anti-tumor responses in HNSCC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Jin Cheng,Shuang Wang,Qianhao Min,Jie Song,Ye Tian
Therapeutic nucleic acid delivery to solid tumors remains a challenge due to enzymatic degradation in cellular uptake and endosomal escape process as well as limited cell permeability. Herein, we reconstructed adoptive-macrophages by integrating functional DNA nanostructure-loaded nucleic acid drugs for tumor immunotherapy. The combination of functional small interfering RNAs (siRNAs) and CpG into DNA tetrahedron (DNA-tet) could induce the repolarization of M2 phenotype macrophages to antitumor M1 type, and releasing proinflammatory cytokines to kill tumor cells. The DNA tet-CpG/siRNA-loaded macrophages show excellent cellular uptake efficiency, parallel delivery capability and induce evident apoptosis and necrosis for tumor cells in vitro. In 4T1 xenograft tumor-bearing mice models, the adoptive macrophage with DNA tet-CpG/siRNA could effectively suppress the growth of subcutaneous tumors persistently and have low side effect for major organs. In summary, our proposed combination therapy of immunological macrophage and DNA-tet-CpG/siRNA will supply new ideas for solid tumor therapy.
研究领域:
癌症治疗
·
纳米技术
·
免疫治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Chendong Yang,Yuanzhan Wang,Yuxue Han,Huiling Dong,Wei Tong,Xuanjun Wu
CpG oligodeoxynucleotides (ODNs) are synthetic Toll-like receptor 9 (TLR9) agonists that promote Th1-biased immune responses. However, their clinical utility is limited by rapid nuclease degradation and poor cellular uptake in antigen-presenting cells (APCs). To overcome this, we developed a pH-responsive nanoadjuvant, Ace-Dex-PC7A@CpG, composed of a cyclic seven-membered tertiary amine-based polymer (PC7A) grafted onto ethoxy-acetalated dextran (Ace-Dex) encapsulating CpG ODN 1668. In vitro, this nanoadjuvant significantly increased the levels of TNF-α, IL-6, IFN-β, and CXCL10 in RAW macrophages, indicating the simultaneous activation of both the TLR9 and stimulator of interferon genes (STING) pathways. In vivo, Ace-Dex-PC7A@CpG significantly enhanced the immunogenicity of the receptor-binding domain (RBD) of SARS-CoV-2, eliciting robust humoral responses with mean anti-RBD IgG titers exceeding 300,000, a 15-fold increase over free RBD (20,000). Sera from immunized mice showed >50% inhibition of RBD-hACE2 binding, far surpassing the 6% inhibition observed with free RBD. Furthermore, in a tumor-associated carbohydrate antigen (TACA) vaccine model, GM2-conjugated bacteriophage MX1 (GM2-MX1) virus-like particles (VLPs) adjuvanted with Ace-Dex-PC7A@CpG produced 10-fold higher anti-GM2 IgG titers than GM2-MX1 alone. More importantly, vaccination with 9NHAc-GD2-mQβ VLPs (a leading TACA vaccine candidate) plus Ace-Dex-PC7A@CpG significantly suppressed liver metastasis in an EL4 lymphoma model. These findings establish Ace-Dex-PC7A@CpG as a versatile nanoadjuvant for subunit vaccines against infectious diseases and cancer.
研究领域:
免疫学
·
纳米技术
·
疫苗学
·
生物化学
·
分子生物学
·
肿瘤学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Qipeng Long,Yang Lin,Jiaqi Zhang,Hengchang Zang,Yan Lu,Yufei Wang,Shulong Jiang
DNA tetrahedron (DT) nanostructures have shown broad application prospects in disease diagnosis and treatment due to their structural programmability, nontoxicity, and efficient cellular uptake. Recently, their potential as ideal nanocarriers for synergistic anticancer drug delivery has been increasingly recognized. In this study, the first use of a DT nanostructure to co-deliver shikonin (SK) and CpG oligonucleotide to achieve chemoimmunotherapy of triple-negative breast cancer (TNBC) is reported. In this nanoplatform, SK serves as both a cytotoxic agent and an immunogenic cell death (ICD) inducer, while CpG-modified DT (CpG-DT) has dual functions of drug carrier and immune adjuvant, which can significantly enhance the ICD effect. CpG-DT/SK exhibits an enhanced water solubility and tumor-specific accumulation. The synergistic combination of SK and CpG further facilitated the maturation of dendritic cells and the subsequent infiltration of CD8+ and CD4+ T cells, thereby achieving effective inhibition of 4T1 tumor growth. This DT-based co-delivery nanoplatform provides a promising strategy for TNBC treatment with great potential for clinical translation.
研究领域:
纳米技术
·
肿瘤学
·
免疫治疗
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 18
·10887
·
IF 6.208
Jing Jie,Guomu Liu,Jingyue Feng,Desheng Huo,Yixuan Wu,Hongyan Yuan,Guixiang Tai,Weihua Ni
Our previous study found that CpG oligodeoxynucleotides 1826 (CpG 1826), combined with mucin 1 (MUC1)-maltose-binding protein (MBP) (M-M), had certain antitumor activity. However, this combination is less than ideal for tumor suppression (tumors vary in size and vary widely among individuals), with a drawback being that CpG 1826 is unstable. To solve these problems, here, we evaluate MF59/CpG 1826 as a compound adjuvant with M-M vaccine on immune response, tumor suppression and survival. The results showed that MF59 could promote the CpG 1826/M-M vaccine-induced tumor growth inhibition and a Th1-prone cellular immune response, as well as reduce the individual differences of tumor growth and prolonged prophylactic and therapeutic mouse survival. Further research showed that MF59 promotes the maturation of DCs stimulated by CpG1826/M-M, resulting in Th1 polarization. The possible mechanism is speculated to be that MF59 could significantly prolong the retention time of CpG 1826, or the combination of CpG 1826 and M-M, as well as downregulate IL-6/STAT3 involved in MF59 combined CpG 1826-induced dendritic cell maturation. This study clarifies the utility of MF59/CpG 1826 as a vaccine compound adjuvant, laying the theoretical basis for the development of a novel M-M vaccine.Keywords:MF59;CpG 1826;compound adjuvant;tumor vaccine;MUC1-MBP;dendritic cells
研究领域:
免疫学
·
肿瘤学
·
疫苗学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Yuying Xu,Minting Liang,Jintao Huang,Yapei Fan,Haiyue Long,Qunjie Chen,Zhe Ren,Chaoxi Wu,Yifei Wang
Single helical β -glucan is a one-dimensional host that can form a hybrid helix with DNAs/RNAs as delivery systems. However, unmodified β -glucan has a gelling tendency and a single helical conformation is challenging to obtain. Therefore, in this study, we developed a β -glucan formyl derivative with stable single helical conformation and no gelling tendency. Circular dichroism studies found that the formyl- β -glucan could form a hybrid helix with DNA CpG-poly(dA). The hybrid helix delivery system showed improved activation on antigen-presenting cells, thereby upregulating the mRNA and protein levels of inflammatory factors, and had an immune-enhancing effect on ovalbumin (OVA) immunized mice. These results indicate that formyl- β -glucan can be developed as a non-cationic supramolecular DNA delivery platform with low toxicity and high efficiency.
研究领域:
生物技术
·
免疫学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2023
·
IF 4.8
Xi Fu,Peng Fu,Tiangui Yang,Tiesheng Niu
Aberrant proliferation and phenotypic switching of vascular smooth muscle cells (VSMCs) are considered to be the main pathological processes of atherosclerotic plaque formation. Methyl-CpG binding protein 2 (MECP2) affects cell differentiation via modulating VSMC-specific gene expression and acts as a driver for the development of atherosclerosis (AS). Here, we aimed to elucidate the role of homeobox A9 (HOXA9) on aberrant VSMCs upon injury or AS, and whether HOXA9-mediated VSMC injury was associated with MECP2. Adeno-associated virus serotype 8-mediated knockdown of HOXA9 rescued aortic pathological injury of apolipoprotein E -deficient (ApoE −/− ) mice fed a high-fat diet (HFD), characterized by the reduction of lipid accumulation and foam cell formation. Further in vitro evidence suggested that proliferation and migration of primary mouse VSMCs (mVSMCs) stimulated by oxidized low-density lipoprotein (ox-LDL) were inhibited after HOXA9 silencing. In addition, HOXA9 silencing blocked VSMC phenotypic switching from contractile to a pathological synthetic state. HOXA9 overexpression caused opposite alterations in ox-LDL-stimulated mVSMCs. Mechanistically, MECP2 was transcriptionally activated by HOXA9. Forced expression of MECP2 impaired the anti-proliferation, anti-migration, and phenotypic switching abilities of HOXA9 silencing in VSMCs upon ox-LDL stimulation. Collectively, our findings reveal that the role of HOXA9 in pathological vascular remodeling may attribute to transcriptional regulation of MECP2.
研究领域:
心血管生物学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Min Zhang,Zhou Fang,Haitao Zhang,Mingxiao Cui,Mingfu Wang,Kehai Liu
In order to reverse tumor immunosuppressive microenvironment and improve antitumor immune effect based on immune checkpoint blocking, a mannose-modified liposome-based CpG ODNs and PD-L1 antagonistic peptides (P) co-delivery system (HA/M-Lipo CpG-P) was constructed, in which hyaluronic acid (HA) coating was supposed to improve the systemic circulation stability and thereby promote its accumulation in tumor tissues. When the HA/M-Lipo CpG-P complexes enter the tumor tissues, HA will be hydrolyzed under the action of hyaluronidase, exposing P peptides. Then, P peptides linked by octapeptides that can be cleaved by matrix metalloproteinases (MMPs) are released into tumor tissues under the action of MMPs, exerting a blocking effect in the PD-1/PD-L1 pathway. The M-Lipo CpG complexes can recognize macrophage surface mannose receptors through its surface modified mannose molecules, and promote the intracellular delivery of CpG ODNs, thereby activating macrophages. The results showed that HA/M-Lipo CpG-P complexes successfully reversed M2-type macrophages in tumor microenvironment (TME) to M1, thereby activating anti-tumor related immune cells and inhibiting tumor growth. Moreover, the HA/M-Lipo CpG-P complexes showed a better tumor inhibitory effect than the HA/M-Lipo CpG or the HA/M-Lipo-P (monotherapy) treatment groups. Overall, HA/M-Lipo CpG-P complexes provide a promising co-delivery strategy for targeting tumors to improve the antitumor effect based on immune checkpoint blockade.
研究领域:
肿瘤学
·
免疫治疗
·
药学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Zhihui Liang,Hang Bao,Zhiying Yao,Min Li,Chen Chen,Lei Zhang,Huiyang Wang,Yiyang Guo,Yubin Ma,Xuecheng Yang,Ge Yu,Jiancheng Zhang,Changying Xue,Bingbing Sun,Chuanbin Mao
In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5′ or 3′ end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3′-end exposure, the 5′-end exposure of CpG in combination adjuvants (Al-CpG-5′) enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5′ enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5′ allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting T fh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines.
研究领域:
免疫学
·
纳米技术
·
疫苗学
·
分子生物学
✓ 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）