Nano Today
·
2024
·
IF 13.2
Wen Li,Qiu-Ling Zhang,Xiang-Yu Ma,Xuan Zeng,Xian-Zheng Zhang
Cancer vaccines have become a milestone in immunotherapy, but inadequate activation rate of antigen presenting cells (APCs) and low delivery efficiency of specific antigen have widely limited their clinical application. Here we design an engineered vaccine platform based on targeted delivery of specific antigens to activated APCs. This vaccine platform is implemented by loading an agonist for stimulator of interferon genes and tumor lysate protein with calcium phosphate as adjuvants, and coating the surface with mannose-modified liposomes. By loading different types of tumor antigen proteins, this nanovaccine platform successfully achieves tumor immunotherapy in breast and colon cancer bearing mice. In addition, personalized nanovaccine prepared from surgically removed tumor lysate proteins also significantly suppresses postsurgical distant tumor. Through the design of nanovaccine platform, we provide an efficient multi-adjuvant delivery platform for multiple types of tumor antigens, and also offer more ideas for personalized vaccine immunization. This nanovaccine platform has great prospects for transformation due to the designability and simplicity for the preparation.
研究领域:
免疫学
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纳米技术
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肿瘤学
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药学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Hangyi Wu,Zhenhai Zhang,Yanni Cao,Yuhan Hu,Yi Li,Lanyi Zhang,Xinyi Cao,Haitong Wen,Youwen Zhang,Huixia Lv,Xin Jin
Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and trigger cuproptosis. However, ES can be rapidly removed and metabolized during intravenous administration, leading to a short half-life and limited tumor accumulation, which hampers its clinical application. Here, the study develops a reactive oxygen species (ROS)-responsive polymer (PCP) based on cinnamaldehyde (CA) and polyethylene glycol (PEG) to encapsulate ES-Cu compound (EC), forming ECPCP. ECPCP significantly prolongs the systemic circulation of EC and enhances its tumor accumulation. After cellular internalization, the PCP coating stimulatingly dissociates exposing to the high-level ROS, and releases ES and Cu, thereby triggering cell death via cuproptosis. Meanwhile, Cu 2+ -stimulated Fenton-like reaction together with CA-stimulated ROS production simultaneously breaks the redox homeostasis, which compensates for the insufficient oxidative stress treated with ES alone, in turn inducing immunogenic cell death of tumor cells, achieving simultaneous cuproptosis and immunotherapy. Furthermore, the excessive ROS accelerates the stimuli-dissociation of ECPCP, forming a positive feedback therapy loop against tumor self-alleviation. Therefore, ECPCP as a nanoplatform for cuproptosis and immunotherapy improves the dual antitumor mechanism of ES and provides a potential optimization for ES clinical application.
研究领域:
药学
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纳米技术
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肿瘤学
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免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 9
·2202710
·
IF 11.092
Jia Wan,Xianghong Zhang,Zhihong Li,Fuhao Mo,Dongsheng Tang,Haihua Xiao,Jingcheng Wang,Guanghua Rong,Tang Liu
Reactive oxygen species (ROS)-induced oxidative stress in the endoplasmic reticulum (ER) is generally believed to be an important prerequisite for immunogenic cell death (ICD) which can trigger antitumor immune responses for cancer immunotherapy. However, thus far, little is known between the oxidative stress in a certain organelle other than ER and ICD. Herein, polymers for preparing ROS-responsive nanoparticles (NP-I-CA-TPP) with mitochondrial targeting performance as ICD nanoinducers are designed. It is believed that NP-I-CA-TPP can target mitochondria which are extremely important organelles intimately involved in cellular stress signaling to play an important role in the induction of ICD. NP-I-CA-TPP can amplify cinnamaldehyde (CA)-induced ROS damage by iodo–thiol click chemistry-mediated glutathione depletion in cancer cells. Finally, NP-I-CA-TPP is shown to disrupt mitochondrial redox homeostasis, amplify mitochondrial oxidative stress, promote cancer cell apoptosis via inducing ICD, and triggering the body's antitumor immune response for cancer immunotherapy.
研究领域:
生物医学工程
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癌症生物学
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免疫学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Bulletin
·
2022
·
IF 20.577
Ruizhi Hu,Chen Dai,Xinyue Dai,Caihong Dong,Hui Huang,Xinran Song,Wei Feng,Li Ding,Yu Chen,Bo Zhang
Iron accumulation and lipid peroxidation form the basis of ferroptosis, potentially circumventing the limitations of apoptosis in cancer treatment. Owing to the lack of potent ferroptosis inducers, the development of efficient ferroptosis-based therapeutic agents and protocols against cancers is highly challenging. Inspired by the topological effect of nanoparticles in modulating cellular function/status, a specific tetrapod ferroptosis-inducer iron-palladium (FePd) nanocrystal was rationally engineered for physically activated autophagy-augmented ferroptosis and enhanced cancer immunotherapy. Specifically, the tetrapod FePd nanocrystal featured strong peroxidase-/glutathione oxidase-mimicking bioactivities, which promoted cancer cell ferroptosis. The special spiky morphology and nanostructure of the FePd nanocrystal simultaneously induced autophagy, which augmented ferroptosis in cancer cells and triggered the release of inflammatory cytokines in macrophages for strengthening anti-PD-L1-antibody mediated immunotherapy, synergistically achieving the maximal antineoplastic effect in three tumor-bearing animal models. This unique physical activation strategy for efficient cancer treatment via precise morphological tuning represents a paradigm for nanomedicine design for efficient tumor treatment.
研究领域:
纳米技术
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癌症研究
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免疫治疗
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Jiahao Hu,Yuchan You,Luwen Zhu,Jucong Zhang,Yanling Song,Jingyi Lu,Xinyi Xu,Xiaochuan Wu,Xiajie Huang,Xiaoling Xu,Yongzhong Du
The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8 + T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.
研究领域:
肿瘤学
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免疫学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-12
·
IF 11.3
Xu Xiaolin,Guan Wencai,Yu Xiaolei,Xu Guoxiong,Wang Chenglong
Background Protocell refers to the basic unit of life and synthetic molecular assembly with cell structure and function. The protocells have great applications in the field of biomedical technology. Simulating the morphology and function of cells is the key to the preparation of protocells. However, some organic solvents used in the preparation process of protocells would damage the function of the bioactive substance. Perfluorocarbon, which has no toxic effect on bioactive substances, is an ideal solvent for protocell preparation. However, perfluorocarbon cannot be emulsified with water because of its inertia. Methods Spheroids can be formed in nature even without emulsification, since liquid can reshape the morphology of the solid phase through the scouring action, even if there is no stable interface between the two phases. Inspired by the formation of natural spheroids such as pebbles, we developed non-interfacial self-assembly (NISA) of microdroplets as a step toward synthetic protocells, in which the inert perfluorocarbon was utilized to reshape the hydrogel through the scouring action. Results The synthetic protocells were successfully obtained by using NISA-based protocell techniques, with the morphology very similar to native cells. Then we simulated the cell transcription process in the synthetic protocell and used the protocell as an mRNA carrier to transfect 293T cells. The results showed that protocells delivered mRNAs, and successfully expressed proteins in 293T cells. Further, we used the NISA method to fabricate an artificial cell by extracting and reassembling the membrane, proteins, and genomes of ovarian cancer cells. The results showed that the recombination of tumor cells was successfully achieved with similar morphology as tumor cells. In addition, the synthetic protocell prepared by the NISA method was used to reverse cancer chemoresistance by restoring cellular calcium homeostasis, which verified the application value of the synthetic protocell as a drug carrier. Conclusion This synthetic protocell fabricated by the NISA method simulates the occurrence and development process of primitive life, which has great potential application value in mRNA vaccine, cancer immunotherapy, and drug delivery. Graphical Abstract
研究领域:
生物技术
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细胞生物学
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分子生物学
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药学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xiaoyu Zhou,Enhui Ma,Yingying Zhang,Yujuan Xing,Wenbei Xu,Liang Chen,Hong Zhou,Xinran Zhang,Canran Jiang,Kai Xu,Hong Wang,Shaohui Zheng
Tumor-associated macrophages (TAMs) always display immunosuppressive M2 phenotype in the tumor microenvironment to facilitate tumor growth, invasion and metastasis. Ibrutinib (IBR), a novel irreversible Bruton's tyrosine kinase (BTK) inhibitor, has been employed to repolarize the BTK-overexpressed TAMs from M2 to M1 phenotype to remodel the immunosuppressive tumor microenvironment. However, the poor solubility of IBR extremely hinders its bioavailability, which results in low tumor accumulation and TAMs uptake in vivo. Herein, we proposed NIR laser-actuated Janus nanomotors for the effective and deep delivery of IBR to TAMs in solid tumor for targeted immunotherapy. Under NIR irradiation, the Janus nanomotors exhibited efficient photothermal conversion to produce powerful propulsion via self-thermophoresis with a speed of 12.15 μm −1 s. Combined with the salic acid targeting and IBR loading, the nanomotors significantly boosted their binding and uptake efficacy by M2-like macrophages during the active motion, which highly facilitated the reprogramming of M2 to M1 macrophages in vitro. Furtherly, the autonomous motion also validly improved in-vivo accumulation and penetration depth in tumors to alter the M1/M2 polarization balance and activate T cells. Overall, the synthesized IC@MSA JNMs would provide a promising strategy for the efficient delivery of immunological agents toward targeted cancer immunotherapy. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
癌症生物学
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免疫治疗
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Xiuhua Pan,Jie Yang,Ruixin Kang,Jun Zhang,Zongwei Hu,Ning Yang,Zengyi Liu,Zengguang Jia,Xiawei Zhou,Qi Shen
The induction of ferroptosis in cancer cells has emerged as a promising approach to initiate immunogenic cell death (ICD). However, the limited production of lipid peroxidation (LPO) considerably undermines the effectiveness of ferroptosis. In this work, T7 polypeptide engineered bacterial outer membrane vesicles (T7-OMVs) co-delivering plasmids and melanin nanoparticles (MNPs) are fabricated into nanoclusters (TO@Mp) for LPO amplification. The clustered regularly interspaced short palindromic repeats (CRISPR) system as the gene editing tool can knockdown glutathione peroxides 4 ( GPX4 ) to amplify LPO accumulation. Photothermal MNPs exhibit an intrinsic capacity of up-regulating Acyl-CoA synthetase long chain family member 4 (ACSL4) and generating reactive oxygen species (ROS), thereby cooperating with GPX4 gene knockdown to reinforce ferroptosis. While the TO@Mp NPs augment ICD via synergistic lipid peroxidation induced ferroptosis, the mechanism of proinflammatory response acquired by the RNA-seq analysis also indicates that the nanoclusters activate the toll like receptor (TLR) pathways, thereby coordinately potentiating DCs maturation and T cells immunity to restrain tumor growth and metastasis. Conclusively, the biomimetic bacteria-derived platform for synergistic CRISPR-photothermo modulation represents an appealing way for tumor suppression and immunological therapy, which holds great potential in clinical translation for cancer treatment.
研究领域:
癌症生物学
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免疫治疗
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纳米技术
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基因编辑
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光热疗法
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jia-Xian Li,Na Shu,Yao-Jun Zhang,Qi-Song Tong,Ling Wang,Jing-Yang Zhang,Jin-Zhi Du
Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitro and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.
研究领域:
药理学
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免疫学
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Huan Liang,Qingqing Lu,Runyu Hu,Yixiao Zhang,Xing Rong,Guocan Yu,Jie Yang
The activation of tumor antigen-specific immune responses is critical for the success of tumor immunotherapy and the advancement of antitumor therapies. However, the limited availability of antigens derived from immunogenic cell death significantly impedes antitumor immunity. To optimize the utilization of the resulting antigens and enhance the tumor-specific immune response, we herein present a strategy that captures antigens in situ within a polymeric depot, facilitated by donor-receptor coordination interactions. An amphiphilic cationic copolymer containing pendant phenylboronic acid (PP) as an electron acceptor unit was synthesized to facilitate various forces with multiple antigens, thereby generating nanovaccines in situ. As the most potent antigen are cell membrane, phenylboronic acid can specifically interact with sialylated epitopes overexpressed on the tumor cell membrane through the formation of donor-receptor coordination. For antigen proteins, the PP could bind with antigens by hydrophobic or electrostatic interaction, thereby facilitating their capture and delivery into the cytosol of antigen-presenting cells (APCs) and activating tumor-specific T cells. This platform could be adapted for various antigens, including antigen protein, tumor lysate and tumor cell membrane, with electron-donating groups, providing a straightforward and robust strategy to enable nanovaccines with enhanced antigen capture capabilities, ultimately improving cancer immunotherapy.
研究领域:
免疫学
·
纳米技术
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肿瘤学
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生物化学
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药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Materials Letters
·
2023
·
IF 11.4
Quan Liu,Zhe Sun,Yanhong Duo,Lei Yin,Kongpeng Lv,Ludan Yue,Qian-Fang Meng,Dingmeng Nie,Jiaojuan Chen,Dixian Luo,Li-Ping Liu,Lang Rao
Immune checkpoint blockade has been regarded as a highly promising cancer immunotherapy approach. However, inefficient immune cell infiltration and the immunosuppressive tumor microenvironment (TME) remain significant causes of low clinical response rates. Here, we identified that trivalent chromium irons (Cr3+) could enhance tumor infiltration of immune cells including M1-type tumor-associated macrophages and CD8+ T cells. Mechanistically, this effect is dependent on the expression of macrophage inflammatory protein-1α (MIP-1α) and the PI3K/Akt/mTOR pathway. Moreover, the Cr-based nanoparticles (Cr NPs) exhibited superior photothermal properties under near-infrared laser irradiation, showing great potential in transforming “cold” tumors into “hot” ones. In combination with the PD-1/PD-L1 pathway inhibitor, we demonstrated that the Cr NPs significantly improved anticancer efficacy in mouse models of hepatoma and melanoma by increasing antitumor immune cell infiltration and relieving immunosuppressive TME. Overall, the Cr NPs offer a new dual-functional platform for local and systemic cancer treatments, paving the way toward cancer photometalloimmunotherapy.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yinghao Ding,Xueying Zhu,Jian Wen,Junchao Xiong,Shengyi Zhang,Zhimou Yang,Zhi-Wen Hu
Antigen presentation deficiency restricted by class I major histocompatibility complex (MHC-I) causes low antigenicity and antigen escape in tumors, thereby limiting T-cell immunotherapy outcomes. Here, a combined tumor immunotherapy is developed, in which tumors can present exogenous non-tumor antigens, and adoptively transferred CD8 + T cells specific for these antigens are re-targeted to attack tumors. The approach leverages a cascade-responsive peptide self-assembly to co-deliver suitable antigens and the chemotherapeutic drug camptothecin (CPT) to tumors. As a proof-of-concept, to re-target ovalbumin (OVA)-specific OT-I CD8 + T cells against tumors, PSA (Nap-GFFpYE-ss-Ag) and CPSA (CPT-GFFpYE-ss-Ag) are constructed, containing an OVA-derived epitope OVA 257-264 and/or CPT. The design enables the release of a unique N-terminal extended OVA 257-264 and CPT into the cytosol. As a result, the extended antigen is efficiently presented on the tumor surface by MHC-I, and CPT further enhances this presentation. When combined with adoptively transferred OT-I CD8 + T cells, the approach effectively facilitates CD8 + T cell infiltration and tumor inhibition. Additionally, CPSA treatment sensitizes immune responses to programmed cell death-ligand 1 (PD-L1) blockade, allowing the approach to synergize with an anti-PD-L1 antibody for improved tumor eradication.
研究领域:
肿瘤免疫学
·
纳米医学
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药物递送系统
·
免疫治疗
·
分子自组装
✓ 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）