ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Xiaohui Chen,Haixia Liu,Ningyu Ma,Chenyu Sun,Yican Li,Hengyi Chen,Qianqian Wu,Zhizeng Wang,Jichun Yang,Guoxiang Liu,Yang Luo
Aberrant methylation of a particular region plays a crucial role in the occurrence and development of malignant tumors. However, the sensitive and precise determination of DNA methylation from clinical samples remains challenging. Here, we developed a sensitive and specific approach for determining methylation with multiple isothermal amplification cascade quantum dot signal output. To increase the sensitivity, an entropy-driven circuit was exploited to specifically recognize the single P16 promoter methylation site and trigger the first amplification, whose product could initiate a hybridization chain reaction for the second amplification. Then, G-quadruplex-rich DNA polymer nanowires were self-assembled, which could bind with quantum dot-labeled TMPyP to turn on the fluorescence, realizing a reliable signal output of trace target. Finally, the proposed approach demonstrated a detection limit of 358.92 aM for the P16 promotor methylation concentration ranging from 1 fM to 1 nM within 1.5 h. In summary, this study provides a sensitive and rapid approach for the determination of methylation via isothermal amplification coupled with quantum dot labeling, paving a new strategy for the early diagnosis and monitoring of cancer development.
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高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Weijian Zhao,Siyu Sun,Xuesong He,Yiran Liu,Jing Meng,Qin Hu,Wang Sheng,Runqing Jia
Nanovaccines represent a promising strategy for colon cancer immunotherapy, with the potential to elicit potent, tumor-specific immune responses. However, the efficacy of these vaccines is often compromised by the presence of cancer stem cells (CSCs) in the tumor microenvironment (TME). Nanoliposome (NLP) is a widely used delivery system in nucleic acid and drug delivery research. In this study, we enriched MC38-derived CSCs (MCSCs) and developed a manganese-CpG-nanoliposome (Mn@CpG@NLP) nanocomplex using MC38 colon carcinoma tumor lysates as antigens to induce immune responses against MCSCs-derived tumors. Manganese NLPs (Mn@NLP) are initially engineered by incorporating manganese ions to enhance their positive surface charge, thereby optimizing their interaction with cellular membranes and activating the STING signaling pathway to promote bone marrow-derived dendritic cells (BMDCs) maturation. Subsequently, these liposomes are co-assembled with the CpG oligonucleotides (CpG ODNs) 1826 adjuvant, a Toll-like receptor 9 agonist, through electrostatic interactions to form the Mn@CpG@NLP nano-adjuvant complex. The Mn@CpG@NLP complex is efficiently taken up by dendritic cells (DCs), leading to their maturation and activation. This nanocomplex also effectively stimulated cytotoxic T lymphocytes and promoted the secretion of cytokines. In vivo treatment with Mn@CpG@NLP significantly inhibited tumor growth and prolonged survival in a mouse model. This study highlights the potential of nano-adjuvant platforms in immunotherapy targeting cancers driven by colon CSCs.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2026
·
IF 7.3
Xiang Yu,Xiaoyao Hao,Hongyan Li,Zemeng Ma,Zhigang Ma,Liezhou Ji,Zhen Yang,Jialong Wang,Mingjiu Chen,Huricha Baigude
CpG oligodeoxynucleotides (CpG ODNs) are short, synthetically produced DNA molecules that serve as classic agonists of Toll-like receptor 9 (TLR9). They are known for their ability to combat infection, alleviate allergic responses, and inhibit tumor growth. However, free CpG is rapidly degraded by nucleases, distributes poorly, and accumulates minimally in tumors. To overcome these limitations, CpG was tethered to tumor-associated antigens or antibodies that engage Fcγ receptors on immune cells in previous studies. Here we redirected CpG toward myeloid cells via SIRPα, an innate immune checkpoint expressed in dendritic cells and macrophages that transmits “don’t-eat-me” signals upon binding tumor-expressed CD47. The conjugate potently matured bone marrow-derived dendritic cells in vitro and, after simple intraperitoneal delivery, safely suppressed tumor growth in vivo. This myeloid-targeted CpG platform broadens the design space for TLR9 agonists and offers an off-the-shelf strategy for integrating innate and adaptive immunity against cancer.
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Small
·
2013
·Vol. 10
·期 2
·368-375
·
IF 7.823
Nan Chen,Min Wei,Yanhong Sun,Fan Li,Hao Pei,Xiaoming Li,Shao Su,Yao He,Lianhui Wang,Jiye Shi,Chunhai Fan,Qing Huang
Synthetic unmethylated cytosine–guanine (CpG) oligodeoxynucleotides (CpG ODNs) possess high immunostimulatory activity and have been widely used as a therapeutic tool for various diseases including infection, allergies, and cancer. A variety of nanocarriers have been developed for intracellular delivery of CpG ODNs that are otherwise nonpermeable through the cellular membrane. For example, previous studies showed that gold nanoparticles (AuNPs) could efficiently deliver synthetic thiolated CpG ODNs into cultured cells and induce expression of proinflammatory cytokines. Nevertheless, the necessity of using thiolated CpG ODNs for the modification of AuNPs inevitably complicates the synthesis of the nanoconjugates and increases the cost. A new approach is demonstrated for facile assembly of AuNP-CpG nanoconjugates for cost-effective drug delivery. It is found that non-thiolated, diblock ODNs containing a CpG motif and a poly-adenine (polyA) tail can readily self-assemble on the surface of AuNPs with controllable and tunable density. Such nanoconjugates are efficiently delivered into RAW264.7 cells and induce immune response in a Toll-like receptor 9 (TLR9)-dependent manner. Under optimal conditions, polyA-CpG-AuNPs show significantly higher immunostimulatory activity than their thiolated counterpart. In addition, the immunostimulatory activity of CpG-AuNPs can be modulated by varying the length of the polyA tail. In vivo induction of immune responses in mice is demonstrated by using polyA-tailed CpG-AuNP nanoconjugates.
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ChemNanoMat
·
2024
·
IF 2.6
Yi Jiang,Chenglun Tang,Yilun Wu,Yishen Zhu
One of the main goals of present vaccine investigations is to develop a potent and efficient adjuvant strategy. The combination of multiple agonists to different pattern recognition receptor families offers great opportunities to achieve strong immune responses in a synergy manner. Here, we employed layered double hydroxide nanomaterials with BSA coating (LB) to integrate CpG and 3pRNA dual adjuvant cocktail, together with ovalbumin antigen. With LB loading, CpG and 3pRNA led to a quick internalization and enhanced induction of dendritic cell (DC) maturation. Meanwhile, this nanoadjuvant cocktail facilitated antigen crosspresenting in activated DCs. Taken together, these results may inspire the investigation of agonists combination and LDH-based nanoadjuvants.
研究领域:
免疫学
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纳米医学
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疫苗研究
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高影响因子
Journal of Biomedical Nanotechnology
·
2018
·Vol. 14
·期 9
·1613-1626
·
IF 5.068
Xia Qingming,Gong Chunai,Gu Fenfen,Wang Zhuo,Hu Chuling,Zhang Lijuan,Qiang Lei,Ding Xueying,Gao Shen,Gao Yuan
Immuno-based oncotherapy has been successfully implemented for cancer treatment. In the present study, we developed a Oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) nano-delivery system based on Multi-walled carbon nanotubes (MWCNTs) conjugated with H3R6
polypeptide (MHR-CpG) for prostate cancer immunotherapy. The in vitro and in vivo toxicity data revealed that the prepared MHR showed high biocompatibility. Confocal laser scanning microscopy confirmed that MHR-CpG could specifically target the endosomal TLR9. In addition, the
use of MHR enhanced the immunogenicity of CpG in both humoral and cellular immune pathways, as evidenced by the increased expression of CD4+ T-cells, CD8+ T-cells, TNF-α, and IL-6. The in vivo anti-cancer efficacy study on RM-1 tumor-bearing mice demonstrated
that MHR-CpG could deliver the immunotherapeutics to the tumor site and the tumor-draining lymph node to suppress tumor growth. These results suggested that MHR-CpG was a promising multifunctional nano system for prostate cancer immunotherapy.
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FISH & SHELLFISH IMMUNOLOGY
·
2026
·
IF 4.2
Wenmei Li,Chenchen Guo,Kaixin Wu,Qunrui Xie,Jianye Yang,Aiwen Shen,Qin Liu,Yuhong Ren
Unmethylated cytosine-guanine oligodeoxyribonucleotides (CpG ODNs) are potent immunostimulants via toll-like receptor 9 (TLR9) recognition, but their application is limited by nuclease degradation and high costs. Herein, a designed ssDNA fragment (1826-F) was circularized with T4 DNA ligase and amplified by rolling-circle amplification (RCA) with Phi29 polymerase, self-assembling into RCA-1826 nanoparticles with a mean size of 63.05 nm and a zeta potential of −5.75 mV. Nuclease resistance assays were performed to evaluate degradation stability, showing RCA-1826 degraded slowly over 24 h while linear control 1826-R was fully degraded within 6 h. In vitro , murine macrophages (RAW264.7) and zebrafish liver cells (ZFL) were treated with RCA-1826, and the results demonstrated that inflammatory factor expression was significantly upregulated, verifying its immunostimulatory activity. In vivo , administration of 1 μg RCA-1826 induced robust innate immunity in zebrafish. Combined with inactivated vaccine, RCA-1826 acted as an effective adjuvant, conferring 94.4% protection against Edwardsiella piscicida . This protection rate is 11.1% higher than that of the sulfur-modified ODN1826-adjuvanted vaccine (83.3%). Overall, RCA-based synthesis enables stable, immunogenic CpG DNA nanoparticles, highlighting RCA-1826 as a promising candidate for E. piscicida prevention in aquaculture.
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BIOMACROMOLECULES
·
2026
·
IF 5.4
Yunan Yuan,Jiaxuan Yang,Yijun Wu,Fujiang Li,Yan Rong,Huayu Tian,Chaoliang He
Chemo-immunotherapy has been an emerging synergistic strategy for melanoma treatment. However, major challenges still remain, including side effects of chemotherapeutic agents and insufficient efficacy of immunotherapy. In the present work, we designed a thermosensitive polypeptide hydrogel-based drug delivery system to achieve the codelivery of doxorubicin (DOX) and a Toll-like receptor (TLR)-9 agonist, CpG. The hydrogel system was engineered by incorporating cancer cell membrane enveloped hollow mesoporous silica loaded with DOX and the mPEG-ss-PEI/CpG nanocomplex, resulting in an enhanced therapeutic effect. Drug-loaded hydrogel system exhibited sustained drug release, enhanced immune cell activation, and induction of immunogenic cell death (ICD) of tumor cells. In vivo antitumor studies revealed that the drug-loaded hydrogel effectively inhibited tumor growth, and promoted expansion of CD8+ T cells and maturation of dendritic cells (DCs), facilitating favorable modulation of the tumor microenvironment. Hence, the developed drug-loaded hydrogel system has considerable potential as a platform for combinatorial chemo-immunotherapy in melanoma treatment.
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高影响因子
Nutrients
·
2023
·Vol. 15
·期 2
·378
·
IF 5.9
Ruizhen Ru,Gengzhan Chen,Xiaoxia Liang,Xudong Cao,Lihong Yuan,Minjie Meng
Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber,Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancer.Keywords:bladder cancer;Frondoside A;CpG oligodexynucleotides;cell viability;apoptosis;cell migration
研究领域:
肿瘤学
·
药理学
·
免疫学
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高影响因子
Advanced Science
·
2025
·
IF 14.1
Jiaqiang Xiong,Juyuan Huang,Hanxiao Xu,Qiuji Wu,Jiahui Zhao,Yurou Chen,Guanlan Fan,Haotong Guan,Rourou Xiao,Zhaojin He,Siqi Wu,Wenliang Ouyang,Shixuan Wang,Lu Zhang,Peng Xia,Wei Zhang,Meng Wu
CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor-associated macrophages (TAMs)into tumoricidal M1 macrophages. However, the accumulation of free CpG in tumor tissues remains a substantial challenge. To address this, a nanovaccine (PLGA-CpG@ID8-M) is engineered by encapsulating CpG within PLGA using ID8 ovarian cancer cell membranes (ID8-M). This nanovaccine demonstrates remarkable efficacy in reprogramming TAMs in ovarian cancer and significantly extends survival in ID8-bearing mice. Notably, these findings indicate that the nanovaccine can also mitigate chemotherapy-induced immunosuppression by increasing the proportion of M1-like TAMs and reducing the expression of CD47 on tumor cells, thereby achieving a synergistic effect in tumor immunotherapy. Mechanistically, through transcriptome sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and mass spectrometry-based proteomics, it is elucidated that the nanovaccine enhances the expression of Gbp2 and promotes the recruitment of Pin1, which activates the NFκB signaling pathway, leading to the M1 polarization of TAMs. Furthermore, macrophages with elevated Gbp2 expression significantly inhibit tumor growth in both ID8 ovarian cancer and 4T1 breast cancer models. Conversely, targeting Gbp2 diminishes the antitumor efficacy of the nanovaccine in vivo. This study offers an innovative approach to immunotherapy and elucidates a novel mechanism (Gbp2-Pin1-NFκB pathway) for remodeling TAMs.
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Materials Today Bio
·
2025
·
IF 10.2
Shaozhen Wang,Chen Yang,Yuanyuan Zhang,Yi Hu,Lan Xiao,Weiping Ding,Bensheng Qiu,Fenfen Li
Cancer immunotherapy encounters challenges of a low treatment response rate due to the tumor immunosuppressive microenvironment and immune-related adverse events caused by off-target immunotherapy agents delivered through systemic administration in clinical practice. Photodynamic therapy (PDT) offers a viable approach to improve the immunotherapy efficacy through inducing immunogenic tumor cell death and is particularly advantageous in superficial tumor treatment. Therefore, leveraging integrated nanomaterials for photo-immunotherapy appears to be an ideal strategy to improve therapeutic outcome. In this study, we develop a transdermal-enhancing peptide (TD)-modified cationic liposome that simultaneously encapsulated with photosensitizer chlorine 6 (Ce6) and immunoadjuvant CpG, denoted as Ce6/CpG@Lip-TD, to mediate photo-immunotherapy of superficial tumors via the skin. The functionalization of TD peptide and positively charged surface endow the liposomes enhanced skin penetration capability. The combination of Ce6 and CpG within the liposomes synergistically potentiates the photo-immunotherapy effect when exposed to laser irradiation. In both melanoma and breast cancer murine models, Ce6/CpG@Lip-TD demonstrated substantial tumor-suppressing properties, along with an augmented systemic immune response against distal tumors. As a topical therapeutic agent, Ce6/CpG@Lip-TD circumvents the regulatory challenges associated with the systemic delivery of nanomaterials and significantly reduces systemic side effects, holding great promise for rapid translation into clinical applications.
研究领域:
肿瘤学
·
纳米医学
·
免疫学
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Theranostics
·
2018
·
IF 8.537
Chunhui Lai,Siliang Duan,Fang Ye,Xiaoqiong Hou,Xi Li,Jin Zhao,Xia Yu,Zixi Hu,Zhuoran Tang,Fengzhen Mo,Xiaomei Yang,Xiaoling Lu
Purpose: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. Methods: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2 180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo. Results: Our results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8 + cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo. Conclusions: The results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.
研究领域:
免疫学
·
肿瘤学
·
药学
·
生物技术
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高影响因子
危险品化学品经营许可证（带存储）