Nature Communications
·
2023
·Vol. 14
·期 1
·1-25
·
IF 16.6
Li Ting,Jiang Shuhui,Zhang Ying,Luo Jie,Li Ming,Ke Hengte,Deng Yibin,Yang Tao,Sun Xiaohui,Chen Huabing
The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor β (TGFβ) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.
研究领域:
肿瘤学
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免疫疗法
·
纳米技术
·
分子生物学
✓ 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
·
癌症研究
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免疫治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2024
·Vol. 9
·期 1
·1-15
·
IF 40.8
Wang Chunling,Xu Junchao,Cheng Xiaoyu,Sun Ge,Li Fenfen,Nie Guangjun,Zhang Yinlong
The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines. Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies, with a primary focus on vascular regulation and stromal reduction. However, these methods may trigger or facilitate tumor metastasis as a tradeoff. Therefore, there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes. As another important factor affecting drug tumor accumulation besides vasculature and stroma, the impact of tumor-associated lymphatic vessels (LVs) has not been widely considered. In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. By combining anlotinib with therapeutic drugs, including doxorubicin (Dox), liposomal doxorubicin (Lip-Dox), and anti-PD-L1 antibody, we observed improved anti-tumor efficacy in comparison with monotherapy regimens. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Xue-Feng Bai,Ying Chen,Mei-Zhen Zou,Chu-Xin Li,Yu Zhang,Min-Jie Li,Si-Xue Cheng,Xian-Zheng Zhang
Recent advances in tumor immunotherapy mainly tend to remodel the immunosuppressive tumor microenvironment (TME) for immune enhancement. However, the complexity of TME makes it unlikely to achieve satisfactory therapeutic effects with any single intervention alone. Here, we focus on exposing intrinsic features of tumor cells to trigger direct pleiotropic antitumor immunity. We develop a photosensitive nanointerferer that is engineered with a nanoscale metal–organic framework decorated with tumor cell membranes for targeted delivery of a photosensitizer and small interfering RNA, which is used to knock down cyclin-dependent kinase 4 (Cdk4). Cdk4 blockade can arrest the cell cycle of tumor cells to facilitate antigen exposure and increase the expression level of programmed cell death protein ligand 1 (PD-L1). Under laser irradiation, photodynamic damage triggered by the nanointerferer induces the release of tumor antigens and recruitment of dendritic cells (DCs), thereby promoting the antitumor activity of CD8+ T cells in combination with anti-PD-L1 antibodies. Ultimately, these events markedly retard tumor progression in a mouse model of ectopic colon tumor with negligible adverse effects. This study provides an alternative treatment for effective antitumor immunity by exciting the intrinsic potential of tumor cells to initiate immune responses while reducing immune-related toxicities.
研究领域:
癌症免疫疗法
·
纳米技术
·
光动力治疗
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Mengqin Gu,Linglin Zhang,Liying Hao,Kun Wang,Wei Yang,Zhenqi Liu,Zixue Lei,Yinmo Zhang,Wei Li,Li Jiang,Xiyu Li
Designing a novel nanoplatform that integrates multimodal imaging and synergistic therapy for precision tumor nanomedicines is challenging. Herein, we prepared rare-earth ion-doped upconversion hydroxyapatite (FYH) nanoparticles as nanocarriers coated and loaded respectively with polydopamine (PDA) and doxorubicin (DOX), i.e., FYH-PDA-DOX, for tumor theranostics. The developed FYH-PDA-DOX complexes exhibited desirable photothermal conversion, pH/near-infrared-irradiation-responsive DOX release, and multimodal upconversion luminescence/computed tomography/magnetic resonance imaging performance and helped monitor the metabolic distribution process of the complexes and provided feedback to the therapeutic effect. Upon 808 nm laser irradiation, the fast release of DOX facilitated the photothermal–chemotherapy effect, immunogenic cell death, and antitumor immune response. On combining with the anti-programmed cell death 1 ligand 1 antibody, an enhanced tri-mode photothermal-chemo-immunotherapy synergistic treatment against tumors can be realized. Thus, this treatment elicited potent antitumor immunity, producing appreciable T-cell cytotoxicity against tumors, amplifying tumor suppression, and extending the survival of mice. Therefore, the FYH-PDA-DOX complexes are promising as a smart nanoplatform for imaging-guided synergistic cancer treatment.
研究领域:
纳米医学
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癌症治疗
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医学成像
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免疫疗法
·
药学
✓ 已验证
DOI
PubMed
高影响因子
Coatings
·
2023
·Vol. 13
·期 8
·1400
·
IF 3.4
Yuyan Peng,Li Jiang,Yifan Li,Xiaoping Yu
Soluble programmed death-ligand 1 (sPD-L1) levels vary widely among different stages of tumor development, so the direct quantification of sPD-L1 as a cancer biomarker is useful in cancer diagnosis, prognosis and therapeutic assessment. There is an urgent need for an sPD-L1 detection method with a broad detection range and high sensitivity for monitoring cancer progression and evaluating the effectiveness of immunotherapy in real time. Herein, we have reported an enzyme-free, label-free surface plasmon resonance imaging (SPRi) sensor based on an aptamer/sPD-L1/anti–PD-L1 sandwich structure with gold nanoparticle (AuNP) signal enhancement for the ultrasensitive quantitative measurement of sPD-L1 for the first time. The gold chip of the SPRi sensing platform was modified by DNA aptamers, sPD-L1 was specifically adsorbed on the surface of a DNA aptamer-modified gold chip and then coupled with anti–PD-L1. Thus, the detection of sPD-L1 at different concentrations was realized through the formation of an aptamer/sPD-L1/anti–PD-L1 sandwich structure. We also enhanced the SPR signal via AuNPs to further improve sensor sensitivity. The SPRi sensor is able to measure sPD-L1 within a linear range of 50 pM–10 nM and 100 fM–50 pM, and the minimum detection limit is 19 fM. The sensor is designed to be widely applicable, with better accuracy and reliability for more application scenarios. The prepared SPRi sensor shows great potential in improving the sensitivity of detecting sPD-L1. The proposed method demonstrates the excellent performance of the SPRi sensor and provides a possibility for the establishment of effective clinical assay methods in the future.Keywords:programmed death-ligand 1;surface sandwich assay;DNA aptamer/antibody bioreceptor pair;surface plasmon resonance;tumor biomarker
研究领域:
癌症生物学
·
生物传感器
·
纳米技术
·
免疫学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 50
·2000335
·
IF 16.836
Qian Cheng,Fan Gao,Wu-Yang Yu,Mei-Zhen Zou,Xing-Lan Ding,Min-Jie Li,Si-Xue Cheng,Xian-Zheng Zhang
The clinical application of antitumor immunotherapy still faces severe challenges related to efficacy. Here, a light-triggered core–shell nanosystem is designed to boost antitumor immune response via controlled release of anti-PD-L1 (αPD-L1) antibodies and enhanced antigen presentation. The nanosystem (AZ-P@P) is constructed via integrating gold nanorods (AuNRs) as a photothermal core and zeolitic imidazolate framework-8 (ZIF-8) as a shell for aPD-L1 delivery, and further PEGylating. In the nanosystem, the ZIF-8 shell protects αPD-L1 antibody from the complex physiological environment and hyperthermia. Once accumulated at the tumor site, AZ-P@P under near-infrared (NIR) light-triggered heating induces tumor cell deaths releasing tumor-derived protein antigens (TDPAs) and adenosine triphosphate (ATP). Thereafter, the released ATP degrades the ZIF-8 shell to expose the AuNRs, which can promote intratumoral T cell infiltration by capturing TDPAs and transporting them to dendritic cells (DCs). Concurrently, a large amount of αPD-L1 is released in situ to reinvigorate T cell activity. Mechanistic studies reveal that AZ-P@P promotes the maturation of DCs and the infiltration of activated T cells, thus eliciting a robust antitumor immunity. It is demonstrated that AZ-P@P triggered by NIR light can significantly destroy primary tumors and suppress metastasis. This multiple immunoregulatory system provides a promising tool for tumor treatment.
研究领域:
癌症免疫治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Caiting Meng,Chenyang Qiao,Qian Hao,Jiahong Shi,Chunju Lou,Jiaqi Song,Leyan Wang,Jinfan Yang,Xiaobin Ma,Huafeng Kang,Hao Wu,Zhengquan Yu,Shuaijun Li
The combination of radiotherapy and immune checkpoint blockade (ICB) therapy has demonstrated considerable efficacy in oncological treatment. However, the clinical PD-L1 antibody (anti-PD-L1) for glioblastoma (GBM) imprecisely accumulated in intracranial radiotherapy target and is often compromised by the formidable blood-brain barrier (BBB). To address these challenges, the study innovatively engineers a hierarchical precision delivery nanoplatform (FB-aPD-L1). This nanoplatform leverages sulfated fucoidan, which exhibited targeted affinity for P-selectin, an adhesion molecule expressed with spatiotemporally restricted specificity in response to radiotherapy. Following precise capture FB-aPD-L1 and crossing BBB, there is ultrasensitive release of BPA 4 -aPD-L1 and fucoidan in the tumor microenvironment. The targeted conjugation of 5-borono-2-pyridinecarboxylic acid (BPA) and sialic acid (SA) augmented tumor-specific targeting and retention of anti-PD-L1, while fucoidan reprogrammed the immune microenvironment, thereby synergizing with the anti-PD-L1 to increase CD8 + T cell infiltration and enhance radio-immunotherapy efficacy. This work exemplifies a novel paradigm for brain-targeted precise drug delivery.
研究领域:
纳米医学
·
肿瘤学
·
免疫治疗
·
放射治疗
·
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
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yilin Yang,Ning Wang,Zhihua Wang,Mingda Han,Fei Yan,Zhan Shi,Shouhua Feng
Sonodynamic therapy (SDT) has emerged as a promising strategy for treating tumors owing to its non-invasiveness and high tissue-penetrating depth. Improving the efficiency of electron-hole separation of sonosensitizers and alleviation of the hypoxic tumor microenvironment remain major challenges. Metal-organic frameworks (MOFs) have greatly potential in SDT application, however, exploring new sonosensitizers with high reactive oxygen species (ROS) generation and improving the efficacy through a synergistic effect in combination with other therapeutic modalities remain major challenges. Furthermore, the immunosuppressive tumor microenvironment (TME) is characterized by hypoxia, which limit the efficacy of O 2 -dependent cancer treatments including SDT and immunotherapy. Herein, we fabricated a defect-rich titanium-based MOFs using propionic acid-mediated self-templated hierarchical etching. Reductive platinum nanoparticles were embedded onto the surface of MOFs to enhance the spatial separation of electron-hole pairs and improve the quantum yield of ultrasound-generated singlet oxygen ( 1 O 2 ). Finally, perfluorobromooctane was encapsulated in the MOFs to function as an oxygen carrier to develop an oxygen self-feeding nanosensitizer. In vitro and in vivo assays demonstrated that this nanoplatform could produce high levels of 1 O 2 under ultrasound irradiation, which led to enhanced SDT. Moreover, this nanoplatform also relieved the immunosuppressive TME by overcoming hypoxia and enhancing immunogenic cell death to promote the infiltration of tumor-specific cytotoxic T cells into the immunologically “cold” tumor. Therefore, combination of nanoplatform-mediated SDT with anti-PDL1 antibodies effectively inhibited the primary tumors, as well as the metastatic tumors. This study provides an insightful strategy for improving SDT and broadens the application of MOF-based sonosensitizers for sono-immunotherapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
材料科学
·
免疫疗法
✓ 已验证
产品关联
DOI
高影响因子
BMC Medicine
·
2022
·Vol. 20
·期 1
·1-18
·
IF 11.15
Cheng Yibin,Wang Caixia,Wang Huihui,Zhang Zhiwei,Yang Xiaopeng,Dong Yanming,Ma Lixin,Luo Jingwen
Background The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect. Methods Here, PD-L1- and CD44-responsive multifunctional nanoparticles were developed using a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). Results PEI-OA greatly improved the drug loading capacity and encapsulation efficiency of the nanoplatform, while the anti-PD-L1 antibody significantly increased its cellular uptake compared to other treatment formulations. Pharmacodynamic experiments confirmed that the anti-PD-L1 antibody can strongly inhibit primary breast cancer and increase levels of CD4+ and CD8+ T cell at the tumor site. In addition, chloroquine reversed the “immune-cold” environment and improved the anti-tumor effect of both chemotherapeutics and immune checkpoint inhibitors, while it induced strong immune memory and prevented lung metastasis. Conclusions Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Jie Zang,Yushan Yang,Xiao Zheng,Yan Yang,Yuge Zhao,Zhe Miao,Tingting Zhang,Jingjing Gu,Yiqiong Liu,Weimin Yin,Xiaoyi Ma,Quanming Ding,Haiqing Dong,Yan Li,Yongyong Li
L-arginine metabolism is essential for the activation, survival, and effector function of the T lymphocytes and critical in eliminating tumors via T-cell-mediated immunotherapy, such as immune checkpoint blockade (ICB). Unfortunately, efficient delivery of hydrophilic L-arginine to the tumor microenvironment (TME) has met tremendous difficulties because of the limited loading efficacy and rapid diffusion. Inspired by the small-molecule prodrug nanoassemblies with ultrahigh drug-loading, we screen out aromatic aldehydes compounds to be used as dynamic tags to decorate L-arginine (reversible imine). Nano-Arginine (ArgNP, 104 nm) was created based on dynamic tag-mediated self-assembly. Molecular dynamics simulations indicate that the driving force of this self-assembly process is intermolecular hydrogen bonds , π–π stacking, and cation–π interactions. Notably, ArgNP metabolic synergy with anti-PD-L1 antibody (aPDL1) can promote tumor-infiltrating T cells (3.3-fold than aPDL1), resulting in a tumor inhibition ratio of 2.6-fold than aPDL1. Besides, such a strategy efficiently reduces the myeloid-derived suppressor cells, increases the M1-macrophages against the tumor, and induces the production of memory T cells. Furthermore, this synergistic therapy effectively restrains lung metastasis and prolongs mouse survival (60% survival ratio). The study highlights the dynamic tags strategy with facility and advance to deliver L-arginine that can metabolically promote ICB therapy.
研究领域:
癌症免疫治疗
·
纳米技术
·
免疫学
·
药物递送系统
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 13
·
IF 11.7
Gongxi Qiao,Shenglin Li,Xumin Pan,Ping Xie,Ruixi Peng,Xiangrong Huang,Mengyun He,Jianhui Jiang,Xia Chu
Directly activating CD8+ T cells within the tumor through antigen-presenting cells (APCs) hold promise for tumor elimination. However, M2-like tumor-associated macrophages (TAMs), the most abundant APCs in tumors, hinder CD8+ T cell activation due to inefficient antigen cross-presentation. Here, we demonstrated a personalized nanotherapeutic platform using surgical tumor–derived galactose ligand–modified cancer cell membrane (CM)–coated cysteine protease inhibitor (E64)–loaded mesoporous silica nanoparticles for postsurgical cancer immunotherapy. The platform targeted M2-like TAMs and released E64 within lysosomes, which reshaped antigen cross-presentation and directly activated CD8+ T cells, thus suppressing B16-OVA melanoma growth. Furthermore, this platform, in combination with anti–PD-L1 antibodies, enhanced the therapeutic efficacy and substantially inhibited 4T1 tumor growth. CMs obtained from surgically resected tumors were used to construct a personalized nanotherapeutic platform, which, in synergy with immune checkpoint blockade (ICB), effectively inhibited postsurgical tumor recurrence in 4T1 tumor. Our work offered a robust, safe strategy for cancer immunotherapy and prevention of postsurgical tumor recurrence.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
肿瘤学
✓ 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）