JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Ziqi Shen,Yueru Pang,Ruixin Kang,Xiawei Zhou,Chao Li,Siyuan Yu,Lin Luo,Feiyang Liu,Jun Zhang,Qi Shen
Fusobacterium nucleatum ( Fn. ) can colonize breast cancer tissue to promote tumor progression by inducing immunosuppression. Targeted therapeutic strategies against intratumoral bacteria remain unexplored and have potential in tumor immunotherapy. Here, a novel biomimetic nanoparticle (FMV@PCFPC) is developed for intratumoral immunosuppressive bacteria clearance and tumor immunogenic cell death (ICD) activation by inducing dual ferroptosis in intratumoral bacteria and tumors. A host-guest complex of hemirotaxane (mPEG-β-CD/α-CD) and polyethyleneimine-ferrocene (Fc-PEI) is constructed, designated as PCFP. PCFP is loaded with antibacterial drug cinnamaldehyde (CA) and wrapped with Fn. -secreted vesicles (FMVs) to form the system FMV@PCFPC. FMVs assist PCFPC in targeting tumors to promote ferrocene and cinnamaldehyde uptake. Fe 2+ in ferrocene, together with glutathione (GSH) -consuming cinnamaldehyde, induces ferroptosis in intratumoral bacteria to relieve tumor immunosuppression. Similarly, PCFPC induces tumor ferroptosis to activate ICD, therefore enhancing antigen presentation and DC maturation. ICD activation works synergistically with intratumoral bacteria clearance to promote cytotoxic T lymphocytes (CTL) activation, inducing robust tumor destruction. Furthermore, killed Fn. bacterial fragments and pathogen-associated molecular patterns (PAMPs) on FMVs function as immunologic adjuvants to further boost immune response. This strategy of intratumoral bacterial clearance and tumor ICD activation relies on dual ferroptosis to effectively enhance anti-tumor immunity, showing great potential in breast cancer treatment.
研究领域:
纳米医学
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癌症免疫学
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微生物学
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生物化学
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药物递送系统
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免疫治疗
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 52
·2106884
·
IF 18.808
Ruoping Wang,Junpeng Shi,Liang Song,Shenghui Zheng,Xiaolong Liu,Maochun Hong,Yun Zhang
Immunotherapy holds great promise for cancer treatment. The key to improving the therapeutic effect is to drive the patient's own immune system to produce a strong, effective, and enduring tumor-specific immune response. Engineered nanoplatforms show promising potential in strengthening antitumor immune responses. However, current nanotherapeutic platforms based on exogenous responses stimulate the immune system only in a transitory and limited manner, which translates into insufficient immune activation and a low therapeutic efficacy. A novel targeted nano-immunostimulant (ZGS-Si-Pc@HA) is fabricated by coupling persistent luminescence nanoparticles with a photosensitizer and hyaluronic acid for sustained immune stimulation upon irradiation with biological window (659 nm) light. ZGS-Si-Pc@HA persistently drives reactive oxygen species production to induce immunogenic cell death, causing a durable tumor-specific immune response. Upon intratumoral injection, ZGS-Si-Pc@HA effectively alleviates immune tolerance and promotes T lymphocyte tumor infiltration. Further, ZGS-Si-Pc@HA enhances the therapeutic effect of checkpoint blockade immunotherapy, effectively inhibiting bilateral tumor growth and triggering an immunological memory effect. Nano-immunostimulants not only provide a new way to boost cancer immunotherapy, but also offer a reliable strategy for fighting cancer metastasis and recurrence clinically.
研究领域:
癌症研究
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纳米技术
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免疫学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Sijia Zhang,Yuanji Feng,Meng Meng,Zhen Li,Huixin Li,Lin Lin,Caina Xu,Jie Chen,Kai Hao,Zhaohui Tang,Huayu Tian,Xuesi Chen
As a representative of tumor immunotherapy, tumor vaccine can inhibit tumor growth by activating tumor-specific immune response, which has the advantages of relatively low toxicity and high efficiency, and has attracted much attention in recent years. However, there are still difficulties in how to effectively deliver tumor vaccines in vivo and make them work efficiently. It is a relatively mature method to load tumor specific antigens with suitable carriers to produce tumor vaccines. Here, a generally minimalist construction method of tumor nanovaccine was developed. A high-efficiency tumor nanovaccine (NV) was prepared in one step by a biomineralization-like method, which contained ovalbumin (OVA, model antigen), unmethylated cytosine-phosphate-guanine (CpG, adjuvant) and Mn-NP (carrier and adjuvant). NV not only showed good tumor preventive effect, but also could successfully inhibited tumor development and metastasis when combined with anti-PD-L1, and induced long-term immune memory effect. However, the method of screening tumor specific antigen to construct nanovaccine is cumbersome and tumors are heterogeneous. Therefore, surgically resected tumor tissue is the best source of antigens for preparing tumor vaccines. Next, based on the strong loading ability of the carrier, we designed a personalized tumor nanovaccine (PNV) using the supernatant of tumor abrasive fluid (STAF) as antigen based on the generally minimalist tumor nanovaccine construction strategy. PNV combined with anti-PD-L1 could successfully inhibit post-surgical tumor recurrence and induce strong and durable immune memory effects. This study presents a novel, general, and minimalist strategy to construct high-efficiency personalized nanovaccine, which has a wide range of potential applications in the field of tumor treatment.
研究领域:
肿瘤学
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免疫学
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Yuxuan Peng,Shuang Liang,Dan Liu,Kongshuo Ma,Kaiqing Yun,Mengli Zhou,Linna Hai,Mengdi Xu,Yiyang Chen,Zhaohui Wang
The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn 2+ and Mg 2+ upon exposure to TME with high levels of H + and H 2 O 2 , which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8 + T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a “hot” network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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治疗开发
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免疫治疗
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肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2022
·
IF 18.962
Hao Tian,Guohao Wang,Wei Sang,Lisi Xie,Zhan Zhang,Wenxi Li,Jie Yan,Ye Tian,Jie Li,Bei Li,Yunlu Dai
Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy . Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn 2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn 2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced cancer immunotherapy.
研究领域:
癌症研究
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免疫学
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纳米技术
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治疗学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Xiaqing Wu,Yan Cheng,Runxiao Zheng,Keqiang Xu,Jiao Yan,Panpan Song,Yanjing Wang,Abdur Rauf,Yue Pan,Haiyuan Zhang
Tumor-associated macrophages (TAMs) of M2 phenotype have mediated the immunosuppression in a tumor microenvironment, facilitating the escape of tumor cells from immunosurveillance. Reprograming the immunosuppressive M2 TAMs to immunostimulatory M1 phenotype can activate the antitumor immune responses for cancer immunotherapy. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were employed to reprogram M2 TAMs toward M1 TAMs, aiming to release proinflammatory cytokines and recruit T cells to kill tumor cells. After loaded with l-arginine (l-Arg) and sealed with poly(acrylic acid) (PAA), hollow Fe3O4 NPs were fabricated into LPFe3O4 NPs, which could release l-Arg based on pH-responsive PAA and produce nitric oxide (NO) with the help of nitric oxide synthase (iNOS) overexpressed by M1 TAMs, as a result of additional tumor elimination for gas therapy. In vitro and in vivo studies demonstrate that LPFe3O4 NPs could effectively reprogram M2 to M1 macrophages, activating T cells, releasing TNF-α, and producing high levels of NO, leading to synergistic tumor therapy.
研究领域:
癌症研究
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纳米技术
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免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yan He,Shiyang Wu,Yibo Yuan,Yueci Sun,Qiangjuan Ai,Ruiqi Zhou,Guozhi Chai,Dawei Chen,Haiyang Hu
Insufficient tumor accumulation and distribution of immunogenic cell death (ICD) inducer as well as low antitumor immunity severely restrict the therapeutic efficacy of tumor immunotherapy . Tumor associated fibroblasts (TAFs) are important in tumor extracellular matrix (ECM) remodeling and immune evasion. Reprogramming tumor immunosuppressive microenvironment via TAFs regulation might present a promising way for enhanced ICD effect and complete tumor elimination. In this study, TAFs derived tryptase imprinted nanoparticles (DMSN@MIPs) are developed to modulate TAFs and improve tumor immunotherapy effect of doxorubicin liposomes (DOX/LIP). Tryptase (TPS), secreted by mast cells, are found to support tumor growth via transcriptionally activating TAFs to an activated state with increased expression of fibroblast activation marker α-smooth muscle actin (α-SMA). DMSN@MIPs canbe used as artificial antibodies, which effectively neutralize TPS, reduce TAFs activation, promote intra-tumor penetration of DOX/LIP and enhance ICD effect induced by DOX/LIP. In addition, the combined administration system remodels immunosuppressive microenvironment, which not only significantly up-regulates immune cells (DC cells, CD8 + T cells , NK cells), but also significantly down-regulates immunosuppressive cells (Treg cells, MDSCs cells). Our results support the DMSN@MIPs canbe a promising approach to improve ICD efficacy in cancer immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
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药学
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Guidong Gong,Qimin Yin,Qinling Liu,Yajing Zhang,Jinyuan Liu,Mengyuan Dai,Jiawen Li,Xianglian He,Jiezhou Pan,Yunxiang He,Bo Wang,Jiyu Tong,Junling Guo
Cells existing in the form of clusters often exhibit distinct biological functions from their single-cell counterparts. However, the ability to modulate cell–cell interactions among multiple cell types through molecular scaffolds remains an ongoing challenge. Here, a supramolecular phenolic network on surfaces of live cells designed is engineered to act as modular scaffolds that promote intercellular interactions, presenting a universal platform for the construction of cell–cell assemblies (CCAs). Utilizing the inherent cell surface affinity of supramolecular phenolic network modules, a series of heterotypic CCAs is efficiently established by assembling five distinct microorganisms and five types of mammalian cells. A specific application of CCAs with the combination of L. casei and macrophages ( L. casei @Mφ) is highlighted for enhanced cancer immunotherapy. Upon intravenous administration, L. casei @Mφ allows the chemotactic Mφ to facilitate the accumulation of L. casei at the tumor. The accumulated L. casei enables the polarization of tumor-associated Mφ toward a pro-inflammatory phenotype, markedly improving the immunotherapeutic response, slowing tumor progression, and mitigating lung metastasis. This work demonstrates the potential of polyphenol-scaffolded modular assembly in manipulating cell–cell interactions to enhance multicellular cooperation, offering a general approach to controlling complex cellular behaviors.
研究领域:
生物医学工程
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免疫学
·
癌症研究
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Kerong Chen,Jielei He,Anwei Zhou,Jiayi Zhu,Shiqin Sheng,Zhen Fu,Xinghai Ning
Sodium overload has emerged as a novel antitumor approach, which is termed as “saltoptosis,” due to its significant therapeutic potential. However, its inherent limitations and related solid tumor treatment challenges have impeded clinical translation. A synergistic strategy integrating saltoptosis with sonodynamic therapy (SDT) is proposed to enhance therapeutic efficacy. Specifically, a M1 macrophage extracellular vesicle-liposome hybrid (termed “Sonophage”), encapsulating sonosensitizer (Ce6), oxygen-enriched perfluorocarbon (PFC-O 2 ), and salt solution (brine), is engineered. This innovative design enables the simultaneous activation of sonodynamic saltoptosis. Under ultrasound, Sonophage directly damages tumor cells via SDT while inducing immunogenic cell death. Concurrently, sodium overload, paired with the biological functions of M1 macrophage extracellular vesicles, reprograms the immunosuppressive tumor microenvironment by polarizing macrophages to a pro-inflammatory M1 phenotype and enhancing T-cell activation, key drivers of antitumor immunity. Additionally, PFC-O 2 alleviates tumor hypoxia, amplifying the combined therapeutic impact. Preclinical studies show that Sonophage selectively targets and penetrates tumors, significantly inhibiting progression, priming systemic immunity to prevent metastasis, and ultimately extending survival. Transcriptomic analysis further confirms its potential to enhance immune responses against tumors. Thus, this combination therapy, where sondynamic waves in a sea of salt orchestrate a synergistic attack on tumors, offers a promising new avenue for advancing cancer treatment.
研究领域:
肿瘤学
·
纳米医学
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免疫治疗
·
生物医学工程
·
分子治疗
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Zhaohan Wei,Xiaoqiong Zhang,Zelong Zhang,Tuying Yong,Guiting Zhan,Weilin Lv,Ziqiao Ding,Kaili Sun,Xiangliang Yang,Lu Gan
Resetting M2-like tumor-associated macrophages (TAMs) to antitumor M1 phenotype is a promising strategy in cancer immunotherapy. Although iron-based nanoparticles exhibit the potential of M2-to-M1 macrophage repolarization, the efficient M2-like TAM targeting and the subsequent intracellular iron retention remains a big challenge. Here, M2 macrophage-targeting peptide-conjugated iron-based metal–organic frameworks are developed to load diclofenac ( [email protected] ) for enhanced cancer immunotherapy. [email protected] efficiently targets M2-like TAMs and decreases the efflux by hepcidin/ferroportin signaling pathway, enabling enhanced intracellular accumulation for improved M2-to-M1 macrophage repolarization. [email protected] M2-like TAMs efficiently kill and phagocytose tumor cells, and importantly remodel tumor immune microenvironment to generate long-term antitumor immune memory, eliciting strong anticancer efficacy with tumor recurrence inhibition. Our results support [email protected] as a potential drug for cancer immunotherapy.
研究领域:
纳米技术
·
免疫学
·
癌症研究
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 21
·2202168
·
IF 32.086
Junli Meng,Peisen Zhang,Qizhe Chen,Zihua Wang,Yuan Gu,Jie Ma,Wang Li,Chen Yang,Yuanyuan Qiao,Yi Hou,Lihong Jing,Yong Wang,Zi Gu,Lichong Zhu,Haozhen Xu,Xueguang Lu,Mingyuan Gao
Nanovaccines have emerged as promising alternatives or complements to conventional cancer treatments. Despite the progresses, specific co-delivery of antigen and adjuvant to their corresponding intracellular destinations for maximizing the activation of antitumor immune responses remains a challenge. Herein, a lipid-coated iron oxide nanoparticle is delivered as nanovaccine (IONP-C/O@LP) that can co-deliver peptide antigen and adjuvant (CpG DNA) into cytosol and lysosomes of dendritic cells (DCs) through both membrane fusion and endosome-mediated endocytosis. Such two-pronged cellular uptake pattern enables IONP-C/O@LP to synergistically activate immature DCs. Iron oxide nanoparticle also exhibits adjuvant effects by generating intracellular reactive oxygen species, which further promotes DC maturation. IONP-C/O@LP accumulated in the DCs of draining lymph nodes effectively increases the antigen-specific T cells in both tumor and spleen, inhibits tumor growth, and improves animal survival. Moreover, it is demonstrated that this nanovaccine is a general platform of delivering clinically relevant peptide antigens derived from human papilloma virus 16 to trigger antigen-specific immune responses in vivo.
研究领域:
纳米技术
·
免疫学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Xueqin Zhu,Xiaoxi Wang,Zimai Liu,Bing Jiang,Zonghong He,Sijia Liu,Yahong Wu,Zixian Wu,Tiantian Zhang,Meiyi Liu,Kai Li,Xiaoshuang Niu,Yanfeng Gao
Although numerous peroxidase (POD)-like nanozymes have been designed for catalytic therapy of cancer, development of nanozymes with higher therapeutic efficacy and less adverse effects are challengeable. More importantly, the underlying antitumor mechanism remains largely unknown which hinders their application. Here, the nitrogen-doped carbon nanozyme (N-PCNS) as a model is utilized and demonstrated that its capacity to specifically activate the STING pathway in tumor cells through reactive oxgen species (ROS)-mediated mitochondrial DNA (mtDNA) release, which provides the initial signals for STING-dependent innate immune response. Further, a peptide-nanozyme conjugate (PNEC, OPBP1-N-PCNS), comprising a PD-L1 blocking/targeting dual-functional peptide and a cationic-coated N-PCNS is constructed, which are conjugated through a matrix metalloproteinase responsive peptide linker. The cleaved derivate nanozyme with positive charge exhibits recyclable capacity and superior ability in capturing and enhancing the transcellular transport of tumor-derived mtDNA toward DCs, thereby amplifying the STING signaling-mediated anti-tumor immune response. This study proposed a unique mechanism and design strategy for POD-like nanozyme in cancer immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）