ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yichi Chen,Wenxin Xu,Huimin Tian,Junbin Gao,Yicheng Ye,Hanfeng Qin,Hong Wang,Yanzhen Song,Chuxiao Shao,Fei Peng,Yingfeng Tu
Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a “cold tumor” into a “hot tumor”, transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
·
光化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Shuojiong Pan,Tianyu Li,Yizheng Tan,Huaping Xu
NK cell-based immunotherapy and pemetrexed (Pem)-based chemotherapy have broad application prospects in cancer treatment. However, the over-expressed NK cell inhibitory receptor on the surface of cancer cells and the low cell internalization efficiency of Pem greatly limit their clinical application. Herein, we construct a series of selenium-containing nanoparticles to synergistically enhance Pem-based chemotherapy and NK cell-based immunotherapy. The nanoparticles could deliver Pem to tumor sites and strengthen the chemotherapy efficiency of Pem by seleninic acid, which is produced by the oxidation of β-seleno ester. Moreover, seleninic acid can block the expression of inhibitory receptors against NK cells, thereby activating the immunocompetence of NK cells. The in vitro and in vivo experiments reveal the potential chemo-enhancing and immune-activating mechanism of seleninic acid, emphasizing the promising prospects of this strategy in effective chemoimmunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫疗法
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药学
·
化疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Junhong Li,Wenxing Lv,Ziwei Han,Yike Li,Jinqi Deng,Yanjuan Huang,Shuo Wan,Jiashu Sun,Bo Dai
Chemo-immunotherapy, combining systemic chemotherapeutic drugs and immune checkpoint blockers, is a promising paradigm in cancer treatment. However, challenges such as limited induction of immune responses and systemic immune toxicity have hindered its clinical applications. Here, a zeolite imidazolate framework-8 (ZIF-8) that encapsulates mitoxantrone (MIT), an immune cell death (ICD)-inducing chemotherapeutic agent (MIT@ZIF-8), is synthesized using a one-pot aqueous-phase process. ZIF-8 serves as a dual-functional nanomaterial for chemo-immunotherapy: a carrier to enhance tumor uptake of MIT for improved chemotherapy efficacy, and a pyroptosis inducer to amplify MIT-induced ICD for augmented anti-tumor immune responses. As a result, in vivo administration of MIT@ZIF-8 markedly inhibits tumor growth in both immunologically “hot” colon cancer and immunologically “cold” prostate cancer. Moreover, MIT@ZIF-8 treatment increases the abundance of cytotoxic CD8 + T cells and reduces the amount of immunosuppressive regulatory T cells in tumors, thereby enhancing anti-tumor immunity and sensitizing prostate cancer to anti-CTLA-4 immunotherapy. In summary, MIT@ZIF-8 offers a highly translational approach for chemo-immunotherapy.
研究领域:
肿瘤学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 7
·3147
·
IF 4.6
Rui Chang,Xiaohong Chu,Jibing Zhang,Rongrong Fu,Changshun Feng,Dianlong Jia,Rui Wang,Hui Yan,Guangyong Li,Jun Li
Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.Keywords:imiquimod;liposome;Fc-CV1;immunotherapy;colon cancer
研究领域:
肿瘤学
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免疫学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Qunfang Yang,Tao Liu,Haiping Zheng,Zechen Zhou,Yan Huang,Honglin Jia,Shixiang Fu,Xuan Zhang,Haigang Zhang,Ya Liu,Xiaohong Chen,Wenjun Shan
The efficacy of immunotherapy combined with other therapeutic modalities in the management of cancer has been extensively studied. However, no effective strategy to improve the antitumor effects of immunotherapy at the tumor site has been developed. In this study, we describe a nanoformulation (CP) that integrates ferroptosis-inducing cannabinoid nanoparticles with immunostimulatory Poly(I:C) to enhance antitumor immune responses by activating ferroptosis-immunotherapy pathways. The results indicated that CP nanoformulation effectively induced ferroptosis , cellular immunogenic death, and anti-tumor immune responses which initiate T cell responses leading to the inhibition of established tumors. In addition, CP nanoformulations reversed the tumor immunosuppressive microenvironment and promoted tumor ferroptosis. These results indicated that the self-amplifying nanoformulation may be an effective strategy for broad-spectrum 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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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Fan Wu,Yu Qian,Chenglong Ge,Yang Zhou,Jing Yan,Xudong Li,Xun Liu,Yuheng Lei,Ziyin Zhao,Yuansong Wei,Junliang Zhu,Lichen Yin,Shanzhou Duan
The anti-tumor efficacy of radiotherapy (RT) is limited by the hypoxic and immunosuppressive tumor microenvironment (TME), which leads to RT resistance and failure in eradicating distant metastatic lesions. Herein, we developed a fluorinated nanosensitizer that could deliver both oxygen (O 2 ) and ADAR1 siRNA into tumor cells to reinforce RT by alleviating hypoxia and immunosuppression. Fluorinated poly(β-amino ester) (fPBAE) was designed to complex ADAR1 siRNA (siADAR1) via electrostatic attraction and load O 2 due to the O 2 -dissolving capacity of fluoroalkyls. The formed nanocomplexes (NCs) facilitated robust cytosolic delivery into cancer cells after intratumoral injection, enabling efficient ADAR1 silencing to promote IFN-β release and enhance DC maturation and T cell infiltration. At the meantime, O 2 was released to alleviate tumoral hypoxia. As thus, NCs significantly enhanced the anti-tumor efficacy of RT and when further coupled with programmed death ligand-1 antibody, they effectively restrained the growth of both treated primary tumors and untreated distant tumors by eliciting robust systemic immune response. This study therefore reports an enlightened strategy for remodeling the immunosuppressive TME and sensitizing radio-immunotherapy. Statement of significance The hypoxic and immunosuppressive tumor microenvironment (TME) greatly limits the anti-tumor efficacy of radiotherapy (RT). To address this critical issue, a nano-sensitizer based on fluorinated poly(β-amino ester) (fPBAE) is herein developed to mediate efficient co-delivery of oxygen (O₂) and ADAR1 siRNA into tumor cells. ADAR1 silencing promotes DC maturation and T cell infiltration to reverse immunosuppression while the released O₂ sensitizes RT. Thus, the nano-sensitizer remarkably enhances the anti-tumor efficacy of RT and elicits robust systemic immune response to eradicate primary and distant tumors when further coupled with PD-L1 antibody.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhen Lin,Fan Nie,Jiantong Hou,Xiaoyang Guo,Xiaotang Gong,Linsu Zhang,Jing Xu,Yuanqiang Guo
Cancer poses a significant threat to human health, and monotherapy frequently fails to achieve optimal therapeutic outcomes. Based on this premise, porphyran (PHP), a marine polysaccharide with immunomodulatory function, was used as a framework to coat gold nanorods and construct a novel nanomedicine (PHP-MPBA-GNRs) combining photothermal therapy and immunotherapy . In this design, PHP not only maintained the dispersion stability and photothermal stability of gold nanorods but also could be released under weakly acidic conditions to activate anti-tumor immunity. In vivo studies have shown that PHP-MPBA-GNRs can effectively inhibit tumor cell proliferation and reduce metastasis under near-infrared (NIR) light irradiation. Preliminary mechanistic investigations revealed that PHP-MPBA-GNRs could increase reactive oxygen species (ROS) and induce apoptosis in cancer cells. The PHP in PHP-MPBA-GNRs can also activate dendritic cells and up-regulate the expression of co-stimulatory molecules and antigen-presenting complexes. All biological experiments, including in vivo tests, demonstrated that PHP-MPBA-GNRs achieved a combination of photothermal therapy and immunotherapy for tumors.
研究领域:
肿瘤学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Wenyan Hao,Nan Sun,Yueyue Fan,Mengyu Chen,Qianqian Liu,Meiyan Yang,Yang Yang,Chunsheng Gao
Ferroptosis therapy and immunotherapy have been widely used in cancer treatment. However, nonselective induction of ferroptosis in tumors is prone to immunosuppression, limiting the therapeutic effect of ferroptosis cancer treatment. To address this issue, this study reports a customized hybrid nanovesicle composed of NK cell-derived extracellular versicles and RSL3-loaded liposomes (hNRVs), aiming to establish a positive cycle between ferroptosis therapy and immunotherapy. Thanks to the enhanced permeability and retention effect and the tumor homing characteristics of NK exosomes, our data indicate that hNRVs can actively accumulate in tumors and enhance cellular uptake. FASL, IFN-γ, and RSL3 are released into the tumor microenvironment, where FASL derived from NK cells effectively lyses tumor cells. RSL3 downregulates the expression of GPX4 in the tumor, leading to the accumulation of LPO and ROS, and promotes ferroptosis in tumor cells. The accumulation of IFN-γ and TNF-α stimulates the maturation of dendritic cells and effectively induces the inactivation of GPX4, promoting lipid peroxidation, making them sensitive to ferroptosis and indirectly promoting the occurrence of ferroptosis. This study highlights the role of the customized hNRV platform in enhancing the effectiveness of synergistic treatment with selective delivery of ferroptosis inducers and immune activation against glioma without causing additional side effects on healthy organs.
研究领域:
肿瘤学
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药理学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
BMC CANCER
·
2025
·Vol. 25
·期 1
·1-10
·
IF 3.4
Liu Shiyuan,Guan Tian,Yang Futian,Zhang Honglei,Yao Yao,Huang Jiman,Zhao Pengfei,Huang Wei,Wu Tailiang,Lin Hui,Fu Ting,Chen Shaoyu,Dai Pengzhan,Ding Zhechun,Chen Dongmei,Li Wei,Zeng Haoyu,Zhang Xianjun
Human oral tongue squamous cell carcinoma (OTSCC) is a prevalent form of head and neck squamous cell carcinoma (HNSCC), often presenting at an advanced stage with a grim prognosis. Traditional therapeutic approaches such as surgery, adjuvant radiotherapy, and chemoradiotherapy have shown limited efficacy in treating advanced OTSCC, underscoring the urgent need for innovative treatment strategies. Our bioinformatics analysis identified CD276 as a significant biomarker in OTSCC, with high protein expression levels correlating to a markedly reduced survival rate in late-stage patients. This discovery has led us to develop chimeric antigen receptor-natural killer (CAR-NK) cells derived from umbilical cord blood cells (UCBCs), specifically targeting CD276. Our aim is to investigate this novel therapeutic approach for its potential to combat OTSCC under pre-clinical conditions. Our in vitro and ex vivo studies have demonstrated that CD276-targeted CAR-NK cells exhibit remarkable efficacy in lysing OTSCC cell lines and primary cells, as well as in eliminating OTSCC organoids. These promising results underscore the pivotal role of CD276 in OTSCC pathogenesis and highlight the potential of CAR-NK cell therapy as a groundbreaking treatment option for advanced-stage OTSCC, offering new hope for translational medicine in the field of stomatology.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yihan Fu,Zichuang Xu,Hengrui Liu,Rongrong Fan,Wenkang Tu,Weili Xue,Xuwu Zhang,Yuchu He,Dawei Gao
Mitochondria, recognized as the cellular powerhouse, provide a continuous stream of energy essential for the rapid proliferation and elevated metabolic demands of tumor cells. Herein, a flexoelectric nanocatalyst, SrTiO₃/RGD/TPP (SRT), is engineered to disrupt mitochondrial proton gradients and ionic balance through ultrasound-induced flexoelectric catalysis. This interference impedes mitochondrial energy production, resulting in tumor cell apoptosis due to an inadequate energy supply. Upon ultrasound stimulation, the SRT experiences polarization due to the stress gradient, resulting in the separation of positive and negative charges, thereby generating a local electric field. The negative charges interact with protons (H⁺) in the mitochondrial intermembrane space to produce hydrogen (H₂), thereby reducing proton concentration and disrupting the mitochondrial proton gradient, subsequently inhibiting ATP synthesis. Concurrently, the local electric field modifies the mitochondrial membrane potential (MMP), opening the mitochondrial calcium uniporter (MCU) channels and facilitating the influx of calcium ions, resulting in calcium overload and mitochondrial dysfunction, ultimately severing the energy supply to tumor cells. This disruption of energy, when combined with immunotherapy, demonstrates significant tumor inhibition in both in vitro and in vivo models. Through the integration of flexoelectric catalysis and immunotherapy, this study demonstrates potent anti-tumor effects and proposes new research directions in nanomedicine.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 5
·1482
·
IF 4.927
Yacong An,Xundou Li,Fengjiao Yao,Jinhong Duan,Xian-Da Yang
The PD-1/PD-L1 pathway blockade can generate a good clinical response by reducing immunosuppression and provoking durable antitumor immunity. In addition to antibodies, aptamers can also block the interaction between PD-1 and PD-L1. For the in vivo application, however, free aptamers are usually too small in size and quickly removed from blood via glomerular filtration. To avoid renal clearance of aptamer, we conjugated the PD-L1 aptamer to albumin to form a larger complex (BSA-Apt) and evaluated whether BSA-Apt would enhance the in vivo antitumor efficacy. The PD-L1 aptamer was thiol-modified and conjugated to the amino group of BSA via a SMCC linker. The average size of BSA-Apt was 11.65 nm, which was above the threshold for renal clearance. Functionally, BSA-Apt retained the capability of the PD-L1 aptamer to bind with PDL1-expressing tumor cells. Moreover, both the free aptamer and BSA-Apt augmented the PBMC-induced antitumor cytotoxicity in vitro. Furthermore, BSA-Apt generated a significantly stronger antitumor efficacy than the free PD-L1 aptamer in vivo without raising systemic toxicity. The results indicate that conjugating the PD-L1 aptamer to albumin may serve as a promising strategy to improve the in vivo functionality of the aptamer and that BSA-Apt may have application potential in cancer immunotherapy.Keywords:PD-L1;aptamer;albumin;BSA-Apt;cancer;immunotherapy
研究领域:
肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-11
·
IF 3.8
Sun Lu,Qi Jun,Ding Lei,Wang Zixuan,Ji Guofeng,Zhang Ping
Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 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）