BIOMATERIALS
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2025
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IF 12.9
Zhanxue Xu,Xinrui Yang,Xingyu Lu,Dandan Su,Yidan Wang,Huixing Wu,Zhenhua Zhang,Changrui Long,Liqian Su,Yanyu Wang,Hongbo Chen,Shijian Xiang,Benjie Zhou
Combination therapies for melanoma face challenges due to asynchronous drug delivery and associated toxicity, underscoring the need for advanced delivery systems. While immune checkpoint inhibitors (ICIs) enhance T cell activity, optimal cytotoxic responses require efficient antigen presentation by mature dendritic cells (DCs), which are often functionally impaired in the tumor microenvironment. Thus, effective treatment requires coordinated T cell activation, DC-mediated priming, and direct tumor suppression. Herein, wild Glycyrrhiza uralensis Fisch roots-derived nanovesicles (GC NV) are demonstrated to be effective inhibitors of melanoma proliferation. The vesicles exert this activity through the intracellular delivery of encapsulated miRNA (miR2916) and bioactive molecules (isoliquiritigenin), with this capacity for intracellular delivery extending to the STING agonist DMXAA. We also demonstrate how chemical modification can be used to install PD-L1 antibodies on the membrane surface of these GC NV, imbuing these vesicles with selectivity for tumor cells. Combining DMXAA encapsulation with surface-displayed PD-L1 antibodies creates vesicles (GP@DMX NV) that both promote DCs maturation and elicit CD8 + T cell response. Our multifunctional GP@DMX NV reverse the immunosuppressive microenvironment of melanoma and significantly enhance the immunotherapeutic potential of immune checkpoints.
研究领域:
肿瘤学
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药剂学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Science China-Materials
·
2021
·Vol. 65
·期 5
·1391-1402
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IF 8.273
Zhang Min,Wang Wenli,Ma He,Yu Bing,Cong Hailin,Shen Youqing
Immunotherapy has shown promising potential in cancer therapy; however, poor delivery by nanocarriers and insufficient immune response in tumors have severely impeded its clinical application. To overcome these disadvantages, a site-specific and active transcellular drug delivery system was developed herein for chemotherapy-enhanced immunotherapy. When arriving at the tumor site, the matrix metallopeptidase 2 (MMP2)-responsive shell detached from the nanosystem, releasing positively charged cores. The cationic surface of the inner cores induced adsorption-meditated transcytosis, which facilitated transendothelial transportation and transcellular drug delivery into distal tumor cells. PD-L1 antibody and chemotherapeutic drugs were loaded in the outer layer and inner cores of the nanosystem, respectively, to be precisely delivered to target sites, thereby achieving synchronized delivery and site-oriented release of different anticancer agents. PD-L1 antibody released in the tumor microenvironment effectively blocked the binding of PD-L1 to its receptors on the T cell surface. Oxaliplatin and indoximod co-delivered in the cationic cores can induce immunogenic cell death and attenuate the immunosuppressive effect throughout the tumor tissues, recruiting a large amount of T cells and further enhancing the immunotherapy. The resulting synergistic antitumor response could not only efficiently inhibit the growth of primary tumors, but also help prevent metastasis of primary tumor to distant sites. This study offers a novel nano-enabled strategy for chemo-immunotherapy in immunosuppressive tumors.
研究领域:
肿瘤学
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纳米医学
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免疫学
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DOI
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 6
·2277-2286
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IF 8.307
Shengran Li,Xintao Xie,Wenliang Wang,Sangni Jiang,Weikang Mei,Yuanhua Zhang,Sanrong Liu,Xifei Yu
Liposomes are used to deliver therapeutics in vivo because of their good biocompatibility, efficient delivery, and ability to protect the therapeutics from degradation. However, the instability of liposomes will cause the therapeutics to lose protection and become ineffective. To deliver therapeutics to the target under guard, we synthesized and used a bio-membrane mimetic choline phosphate lipid (CP-lip) to intra-crosslink liposomes to highly improve their stability. We found that when the ratio of PC-lip to CP-lip is 1 : 2, the intra-crosslinked liposome (PC–CP-lipo) showed higher stability, better biocompatibility and improved anti-protein adsorption than other common liposomes. We used doxorubicin (Dox) loaded PC–CP-lipo to treat melanoma and the tumor inhibition ratio could reach 86.3%. After the combined Dox@PC–CP-lipo treatment with PD-L1 antibody to block the immune checkpoints, the tumor suppression rate could reach 94.4%, and 60% of the mice did not suffer from tumor rechallenge. The method of using a CP-lip to intra-crosslink liposomes is applicable to all liposomes, solving the key problem of liposome disintegration, thus enhancing the protection of drugs and antibodies by liposomes in vivo.
研究领域:
药学
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生物技术
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Yu Hei,Binhong Teng,Ziqian Zeng,Siqi Zhang,Qian Li,Jijia Pan,Zuyuan Luo,Chunyang Xiong,Shicheng Wei
Background Immune checkpoint blockades (ICBs) are a promising treatment for cancers such as melanoma by blocking important inhibitory pathways that enable tumor cells to evade immune attack. Programmed death ligand 1 monoclonal antibodies (aPDL1s) can be used as an ICB to significantly enhance the effectiveness of tumor immunotherapy by blocking the PD-1/PD-L1 inhibitory pathway. However, the effectiveness of aPDL1s may be limited by low selectivity in vivo and immunosuppressed tumor microenvironment including hypoxia.Purpose To overcome the limitations, we develop a multifunctional immunoliposome, called CAT@aPDL1-SSL, with catalase (CAT) encapsulated inside to overcome tumor hypoxia and aPDL1s modified on the surface to enhance immunotherapeutic effects against melanoma.Methods The multifunctional immunoliposomes (CAT@aPDL1-SSLs) are prepared using the film dispersion/post-insertion method. The efficacy of CAT@aPDL1-SSLs is verified by multiple experiments in vivo and in vitro.Results The results of this study suggest that the multifunctional immunoliposomes preserve and protect the enzyme activity of CAT and ameliorate tumor hypoxia. Moreover, the enhanced cellular uptake of CAT@aPDL1-SSLs in vitro and their in vivo biodistribution suggest that CAT@aPDL1-SSLs have great targeting ability,resulting in improved delivery and accumulation of immunoliposomes in tumor tissue.Finally, by activating and increasing the infiltration of CD8+ T cells at the tumor site, CAT@aPDL1-SSLs inhibit the growth of tumor and prolong survival time of mice,with low systemic toxicity.Conclusion In conclusion, the multifunctional immunoliposomes developed and proposed in this study are a promising candidate for melanoma immunotherapy, and could potentially be combined with other cancer therapies like radiotherapy and chemotherapy to produce positive outcomes.
研究领域:
肿瘤学
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免疫学
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药学
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生物技术
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产品关联
DOI
PubMed
高影响因子
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
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2023
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IF 14
Zhuoya Gao,Jiarong Zhang,Yingchao Hou,Jinjin Lu,Jing Liang,Yufeng Gao,Boqi Li,Shuai Gao,Yanjun Zhao,Min Gao,Jinghua Chen
Both ferroptotic therapy and immunotherapy have been widely employed in cancer treatment. However, ferroptotic cell death fails to induce dendritic cells maturation, which limits the therapeutic outcome of ferroptotic cancer therapy. To address this, the current work reports a tailored liposome to establish a positive loop between ferroptotic therapy and immunotherapy. As the key component of liposome, a unique phospholipid is designed to bear two arachidonic acid tails. The liposome is further surface-engineered with fucose ligand and physically encapsulates immunostimulatory CpG oligodeoxynucleotides (ODNs). The tailored liposome shows enhanced cellular uptake in a model 4T1 cell line. Meanwhile, the high level of reactive oxygen species in cancer cells can induce ferroptosis-specific peroxidation of DAPC and trigger the release CpG ODNs. The CpG ODNs further enable the maturation of dendritic cells and enhance the effector function of CD8 + T cells . IFN-γ released from CD8 + T cells promotes cancer cell ferroptosis via inhibiting SLC7A11 and suppressing the biosynthesis of glutathione . The tailored liposome can also act in synergism with PD-L1 antibody, resulting in enhanced anti-cancer efficacy in a 4T1 tumor-bearing mice model. This work provides a promising strategy for cancer treatment through orchestrating ferroptotic therapy and immunotherapy.
研究领域:
肿瘤学
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药学
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免疫学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Fundamental Research
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2023
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IF 6.2
Zhuo Cheng,Yan Hu,Yingqi Liu,Xuan Wang,Rui Xue,Kaiyong Cai,Liqi Li,Menghuan Li,Zhong Luo
ABSTRACT Post-resection tumors with microscopic foci and immunosuppressive microenvironments have high risk of recurrence and metastasis but respond poorly to various therapies. Herein, we propose a biomimetic hydrogel as a biocompatible, biodegradable and bioadhesive postoperative dressing that could be formed in situ by NaIO 4 -initiated thiourea-catechol crosslinking after syringe-injection into the resection cavity. The thiourea or catechol-bearing hyaluronic acid (HA) precursors are also separately engineered with phenylboronic acid and β-cyclodextrin (β-CD) groups, potentiating the reversible immobilization of (1S, 3R) RAS-selective lethal 3 (RSL3) and glycosylated granulocyte macrophage-colony stimulating factor (GM-CSF) without invasive chemical reactions. Meanwhile, the interconnected porous superstructure of the hydrogels allows the incorporation and self-regulated delivery of PD-L1 antibody (aPD-L1). RSL3-induced immunogenic ferroptosis and GM-CSF could cooperatively trigger robust adaptive tumor-specific immune responses, while aPD-L1 further alleviates the accumulated immunoresistance of tumor cells due to interferon γ-mediated PD-L1 upregulation, thus stimulating potent local and whole-body antitumor immunity to prevent postoperative tumor recurrence and metastasis. The biomimetic hydrogel may serve as a promising solution for the postoperative treatment of solid tumors.
研究领域:
生物医学工程
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免疫疗法
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癌症研究
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材料科学
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产品关联
DOI
高影响因子
Science Bulletin
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2022
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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
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
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药理学
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免疫学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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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
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纳米技术
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光动力治疗
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 18
·期 9
·2105118
·
IF 13.281
Yu Hei,Yang Chen,Qian Li,Zi Mei,Jijia Pan,Siqi Zhang,Chunyang Xiong,Xiaodong Su,Shicheng Wei
The immunosuppressive tumor microenvironment (TME) can significantly limit the immunotherapeutic effects of the PD-L1 antibody (aPDL1) by inhibiting the infiltration of CD8 + cytotoxic T cells (CTLs) into the tumor tissues. However, how to reprogram the immunosuppressive TME and promote the infiltration of CTLs remains a huge challenge for aPDL1 to achieve the maximum benefits. Herein, the authors design a multifunctional immunoliposome that encapsulates the adrenergic receptor blocker carvedilol (CAR) and connects the “don't eat me” signal antibody (aCD47) and aPDL1 in series via a reactive oxygen species (ROS)-sensitive linker on the surface. In ROS-enriched immunosuppressive TME, the multifunctional immunoliposome (CAR@aCD47/aPDL1-SSL) can first release the outer aCD47 to block the “do not eat me” pathway, promote the phagocytosis of tumor cells by phagocytic cells, and activate CTLs. Then, the aPDL1 on the liposome surface is exposed to block the PD-1/PD-L1 signaling pathway, thereby inducing CTLs to kill tumor cells. CAR encapsulated in CAR@aCD47/aPDL1-SSL can block the adrenergic nerves in the tumor tissues and reduce their densities, thereby inhibiting angiogenesis in the tumor tissues and reprogramming the immunosuppressive TME. According to the results, CAR@aCD47/aPDL1-SSL holds an effective way to reprogram the immunosuppressive TME and significantly enhance immunotherapeutic efficiency of aPDL1 against the primary cancer and metastasis.
研究领域:
癌症免疫疗法
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药学
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生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Coatings
·
2023
·Vol. 13
·期 8
·1400
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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
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生物传感器
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纳米技术
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免疫学
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分析化学
✓ 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）