JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Maoyu Gao,Kai Feng,Xinmiao Zhang,Yiling Ruan,Guizhen Zhao,Huihui Liu,Xiaolian Sun
Cancer immunotherapy is an emerging cancer therapeutic method by activating the patient's immune system but suffers from low immunogenicity at tumor sites. Fever-like heat is known to modulate an immune-friendly tumor microenvironment . Here, temperature-responsive iron oxide nanoassemblies (IONAs) are developed by crosslinking iron oxide nanoparticles (IONPs) and loaded with JQ1 (JQ1/IONAs), an immuno-modulating agent known to down-regulate PD-L1. In the presence of an alternating magnetic field (AMF), the IONAs demonstrate a much more effective magnetic thermal effect than IONPs and are responsively disassembled to prevent overheating. Compared with IONPs + AMF (∼ 41 °C) and unresponsive nanoassemblies (uIONAs) + AMF (∼ 50 °C), the IONAs + AMF with a temperature heated around 45 °C show a much better immune response and anti-tumor effect. Further combining the mild thermal therapy with controlled release of JQ1, the JQ1/IONAs + AMF completely eradicate the primary tumors and trigger a strong immune effect to inhibit the distant tumor growth as well as prevent tumor recurrence and metastasis. Our JQ1/IONAs not only provide a magnetic thermal agent with effective heating and temperature self-regulation ability but also serve as a heat-triggered JQ1 carrier to spontaneously combine mild magnetic thermal therapy with immune checkpoint blockade therapy.
研究领域:
纳米技术
·
肿瘤学
·
免疫治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Qi Long,Yuliang Yang,Fangling Liao,Haoting Chen,Dongyue He,Shengliang Li,Li Pengcheng,Weisheng Guo,Yafang Xiao
Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cells (DCs) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor the therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost adaptive anti-tumor immunity of photothermal immunotherapy and achieve multiple bioimaging modalities in a real-time manner. The PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cells maturation and T cell recruitment. Meanwhile, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.
研究领域:
生物医学工程
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癌症研究
·
免疫治疗
·
纳米技术
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Yu-Rong Zhan,Xi He,Zhi-Ying Huang,Ping Chen,Miao-Miao Tian,Guo-Hong Li,Xiao-Qi Yu,Xiang-Rong Song,Ji Zhang
The inefficient treatment using protein-based nanovaccines is largely attributed to their inadequate immunogenicity. Herein, we developed a novel fluoropolymer (PF) via ring-opening polymerization and constructed a fluoropolymer-based nanovaccine for tumor immunotherapy. Due to the existence of fluoroalkyl chains, PF not only played a crucial role in tumor antigen delivery but also exhibited a remarkable adjuvant effect in enhancing the immunogenicity of nanovaccines. The nanovaccines formed by mixing PF with a model antigen ovalbumin (OVA) enhanced the uptake of antigen proteins by dendritic cells (DCs) and promoted the maturation and antigen presentation of DCs. Compared with free OVA, PF/OVA showed better efficacy in both pre-cancer prevention and tumor treatment. Furthermore, the proportion of CD4+ T and CD8+ T cells was significantly increased in lymph nodes and tumors of mice immunized with PF/OVA. Additionally, there was a great enhancement in the levels of key anti-tumor cytokines (TNF-α and IFN-γ) in the serum of the PF/OVA immunized mice. Our research has shown that fluoropolymer PF applied as a protein vector and adjuvant has great potential for the development of nanovaccines with robust immunogenicity.
研究领域:
癌症免疫学
·
药学
·
纳米技术
·
免疫治疗
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Yang Liu,Hui Li,Yan-Yun Hao,Ling-Ling Huang,Xia Li,Jing Zou,Shi-Ying Zhang,Xiao-Yue Yang,Hong-Fei Chen,Yi-Xuan Guo,Yun-Yan Guan,Zhi-Yue Zhang
The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed. By using the tumor-targeting properties of c-RGD, the system can effectively deliver monocarboxylate transporters 4 (MCT4) inhibitor (Syro) to inhibit lactate efflux in tumor cells, leading to decreased lactate levels in the tumor microenvironment (TME) and increased accumulation within tumor cells. The reduction of lactate in TME will reduce the nutritional support for regulatory T cells (Tregs) and promote the effector function of T cells. The accumulation of lactate in tumor cells will lead to tumor death due to cellular acidosis. In addition, it will also reduce the uptake of glucose by tumor cells, reduce nutrient plunder, and further weaken the inhibition of T cell function. Furthermore, the pH-responsive release of Toll-like receptors (TLR) 7/8 agonist IMDQ within the TME activates dendritic cells (DCs) and promotes the infiltration of T cells. These findings offer a promising approach for enhancing tumor immune response through targeted metabolic interventions.
研究领域:
癌症生物学
·
免疫学
·
纳米技术
·
代谢工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Immunology Research
·
2024
·
IF 8.1
Shi Yongjing,Zheng Xiaodong,Peng Hui,Xu Chenqi,Sun Rui,Tian Zhigang,Sun Haoyu,Wang Xianwei
Natural killer (NK) cells are the main innate antitumor effector cells but their function is often constrained in the tumor microenvironment (TME). It has been reported that the E3 ligase FBXO38 accelerates PD-1 degradation in tumor-infiltrating T cells to unleash their cytotoxic function. In this study, we found that the transcriptional levels of FBXO38 in intratumoral NK cells of cancer patients and tumor-bearing mice were significantly lower than in peritumoral NK cells. Conditional knock-out (cKO) of FBXO38 in NK cells accelerated tumor growth and increased tumor metastasis. FBXO38 deficiency resulted in impaired proliferation and survival of tumor-infiltrating NK (TINK) cells. Mechanistically, FBXO38 deficiency enhanced TGF-β signaling, including elevating expression of Smad2 and Smad3, which suppressed expression of the transcription factor Eomes and further reduced expression of surface IL-15Rβ and IL-15Rγc on NK cells. Consequently, FBXO38 deficiency led to TINK cell hyporesponsiveness to IL-15. Consistent with these observations, FBXO38 mRNA expression was positively correlated with the proliferation of TINK cells in multiple human tumors. To study the therapeutic potential of FBXO38, mice bearing human tumors were treated with FBXO38 overexpressed human primary NK cells and showed a significant reduction in tumor size and prolonged survival. In conclusion, our results suggest that FBXO38 sustains NK-cell expansion and survival to promote antitumor immunity, and have potential therapeutic implications as they suggest FBXO38 could be harnessed to enhance NK cell–based cancer immunotherapy.
研究领域:
癌症生物学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Doudou Hu,Hongxia Xu,Wei Zhang,Xiaodan Xu,Bing Xiao,Xueying Shi,Zhuxian Zhou,Nigel K.H. Slater,Youqing Shen,Jianbin Tang
Conventional photothermal therapy (PTT) is insufficient to induce a strong and potent anti-tumor immune response. Herein, we present a vanadyl nanocomplex, which simultaneously serves as a photothermal agent (PTA) and an immunogenic cell death (ICD) inducer to enhance the anti-tumor immunity of PTT. The vanadyl nanocomplex (STVN) is constructed via facile one-step coordination assembly under ambient conditions. STVN not only has a strong and stable photothermal effect under near-infrared (NIR) irradiation, but also can cause severe endoplasmic reticulum (ER) stress by itself, leading to ICD and activating the systemic immune responses. In the absence of any adjuvants, NIR-irradiated STVN almost completely ablates primary tumors and simultaneously inhibits distant tumors in mice bearing bilateral melanoma. Meanwhile, the intratumorally injected STVN combined with NIR effectively suppressed melanoma lung metastasis as well as tumor recurrence, displaying that local STVN-mediated PTT could trigger a systemic anti-tumor immunity. Therefore, STVN, as a novel immunogenicity-enhanced PTA, affords a “one stone two birds” strategy for improved photothermia-induced cancer immunotherapy .
研究领域:
癌症研究
·
纳米技术
·
免疫治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Mengyue Pei,Rong Xu,Chuangnian Zhang,Xiaoli Wang,Chen Li,Yunzhang Hu
Cancer immunotherapy is an important tumor therapy option for prevention and treatment of tumors and has attracted tremendous interests. However, the therapeutic outcomes are limited by insufficient antigen uptake and presentation by antigen-presenting cells such as dendritic cells (DCs). In this study, mannose-functionalized antigen nanoparticles with endosome escape activity were designed for targeted DCs, accelerated endosomal escape and enhanced MHC-I antigen presentation for cancer immunotherapy. Mannose was selected as DCs targeting ligand to enhance antigen uptake. Model antigen ovalbumin (OVA) was directly conjugated with mannose to obtain DCs targeting antigen, which was then complexed with polyethylenimine (PEI) through electrostatic interaction to form mannose-functionalized antigen nanoparticles (MAN-OVA/PEI NPs). Flow cytometry analysis revealed that the MAN-OVA/PEI NPs greatly increased antigen uptake by DCs compared with OVA/PEI NPs. Confocal laser scanning microscopy further demonstrated that MAN-OVA/PEI NPs enhanced cytosolic antigen release. Moreover, MAN-OVA/PEI NPs significantly promoted cytokine production and DCs maturation in vitro . More importantly, MAN-OVA/PEI NPs treated DCs exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro . This work suggests that mannose-functionalized antigen nanoparticles provide a versatile delivery vehicle for targeted DCs, accelerated endosomal escape and enhanced MHC-I antigen presentation for cancer immunotherapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2023
·
IF 9.9
Peng Yiwei,Yang Yiliang,Yang Zhenzhen,Gao Datong,Li Jiajia,Sun Qi,Du Yitian,Lin Meng,Qi Xianrong
Immunotherapy has great promise in improving malignant tumor treatment. However, the efficacy of existing strategies is often limited by the immunosuppressive environment. Here, we demonstrate an in situ bionic immunoactivator, PLT-Bec1/DTA-1, with possessed natural advantages of platelets for tumor recruitment and activation, on which DTA-1 (CD357 monoclonal antibody) and Bec1 were tethered as combined immune boosters. PLT-Bec1/DTA-1, as a self-triggered release repository, can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles (PMPs), thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells (DCs) and T cells via autophagy inducibility, coupled with glucocorticoid-induced tumor necrosis factor receptor (GITR)-triggered T Reg suppression, remodeled the immunosuppressive network of tumor microenvironment. PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation, and alleviated the low activity state of bone marrow-derived dendritic cells (BMDCs) in tumor suppressive environment. PLT-Bec1/DTA-1 inhibited tumor recurrence (5- and 13-fold lower of control group in tumor volume) and CD8 + T/T Reg ratio (6.3- and 8.8-fold vs. control group) in mouse tumor model after intravenous or subcutaneous administration. Also, PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation, and was slightly superior to the combined of Bec1 and PD-L1. Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers, eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication. All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.
研究领域:
癌症免疫治疗
·
生物医学工程
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 16
·4549-4560
·
IF 7.59
Ying Qian,Jiarong Mao,Xuejiao Leng,Ling Zhu,Xue Rui,Zhetong Jin,Houzhe Jiang,Heng Liu,Fengguang Zhang,Xiaolin Bi,Zhipeng Chen,Jingjing Wang
Immunological checkpoint inhibitors provide a revolutionary method for cancer treatment. However, due to low tumor mutations and insufficient infiltration of immune cells into the tumor microenvironment, 85% of colorectal cancer patients cannot respond to checkpoint blockade immunotherapy. In this study, tumor microenvironment-responsive deformable nanoparticles (DMP@NPs) were rationally designed to improve immunotherapy by synergistically modulating the immune tumor microenvironment. DMP@NPs self-assemble from a newly synthesized tumor acidity responsive polypeptide checkpoint inhibitor polymer (PEG–DMA–DPPA-1) with immunogenic cell death (ICD) enhanced combination drugs containing a certain proportion of mitoxantrone (MITX) and proanthocyanidins (PC). Upon tumor acidity-triggered cleavage of PEG–DMA–DPPA-1, DMP@NPs undergo special “sphere-ring deformation” dissociation, gradually releasing polypeptide checkpoint inhibitor DPPA-1, MITX and PC. MITX/PC in vitro synergistically triggers higher ICD with the release of the high mobility group box-1 (HMGB-1) and calreticulin (CRT). After intravenous injection of DMP@NPs, the local tumor microenvironment of CT26 tumor-bearing mice was reprogrammed, and dendritic cell activation and T cell infiltration were significantly increased. Most importantly, the synergistic immune nanodrug DMP@NPs improved the efficacy of colorectal cancer immunotherapy and reduced toxicity and side effects for the immune organs.
研究领域:
肿瘤学
·
药学
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Dandan Jiang,Tong Gao,Shuang Liang,Weiwei Mu,Shunli Fu,Yang Liu,Rui Yang,Zipeng Zhang,Yongjun Liu,Na Zhang
Lymph nodes are the main sites for immune activation and surveillance. Effective delivery of immunomodulators into lymph nodes to trigger antitumor immunity is essential for cancer treatment. Here, we propose a lymph node delivery strategy to modulate the immune response by activating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells simultaneously. Novel pH/redox dual-sensitive micelles were prepared using poly(l-histidine)-poly(ethylene glycol) (PLH-PEG) as a skeleton, which can effectively deliver immunomodulators to the lymph nodes due to their suitable particle size. At 48 h after subcutaneous injection, the accumulation efficiency in lymph nodes increased 8.12-fold compared with the control group. Subsequently, Trp2/CpG-coloaded pH/redox dual-sensitive micelles (Trp2/CpG-NPs) acted on antigen-presenting cells, fully promoting CTL activation through dendritic cell antigen cross-presentation and macrophage repolarization. IL-15-loaded pH/redox dual-sensitive micelles (IL-15-NPs) were developed to activate the killing effect of NK cells by interacting with IL-15 receptors. In the tumor-bearing mice model, this lymph node delivery strategy showed significant antitumor efficiency and the tumor inhibition rate reached 93.76%. Meanwhile, the infiltration of CTLs and NK cells in tumor tissues increased, and the immunosuppressive microenvironment was relieved by the repolarization of macrophages from M2-type to M1-type. Overall, this study highlighted the potential of the lymph node delivery strategy for cancer immunotherapy.
研究领域:
癌症免疫治疗
·
免疫学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
·
癌症免疫学
·
微生物学
·
生物化学
·
药物递送系统
·
免疫治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Sixin Xu,Lingkai Meng,Qian Hu,Fang Li,Jieying Zhang,Na Kong,Zhenyu Xing,Guosong Hong,Xingjun Zhu
Macrophage engineering has emerged as a promising approach for modulating the anti-tumor immune response in cancer therapy. However, the spatiotemporal control and real-time feedback of macrophage regulatory process is still challenging, leading to off-targeting effect and delayed efficacy monitoring therefore raising risk of immune overactivation and serious side effects. Herein, a focused ultrasound responsive immunomodulator-loaded optical nanoplatform (FUSION) is designed to achieve spatiotemporal control and status reporting of macrophage engineering in vivo. Under the stimulation of focused ultrasound (FUS), the immune agonist encapsulated in FUSION can be released to induce selective macrophage M1 phenotype differentiation at tumor site and the near-infrared mechanoluminescence of FUSION is generated simultaneously to indicate the initiation of immune activation. Meanwhile, the persistent luminescence of FUSION is enhanced due to hydroxyl radical generation in the pro-inflammatory M1 macrophages, which can report the effectiveness of macrophage regulation. Then, macrophages labeled with FUSION as a living immunotherapeutic agent (FUSION-M) are utilized for tumor targeting and focused ultrasound activated, immune cell-based cancer therapy. By combining the on-demand activation and feedback to form a closed loop, the nanoplatform in this work holds promise in advancing the controllability of macrophage engineering and cancer immunotherapy for precision medicine.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
免疫学
·
诊疗学
✓ 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）