JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ming Zhao,Chunting He,Xueyun Zheng,Min Jiang,Zhiqiang Xie,Hongjiao Wei,Shujun Zhang,Ying Lin,Jiaheng Zhang,Xun Sun
Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (−1.18 mV) following encapsulation, referred to as n( OVA )C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8 + T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.
研究领域:
免疫学
·
疫苗开发
·
纳米技术
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·
IF 3.7
Lida Feng,Guixiao Huang,Qifang Lei,Mingkang Liang,Dashi Deng,Xiaocen Liu,Chenfan Kong,Chenchen Li,Xiyang Tan,Guangzhi Li,Song Wu
Intravesical instillation-based immunotherapy for bladder-preservation of bladder cancer (BCa) treatment has not been explored. In the current study, two irrigated nano-formulations of immunological adjuvant-fluorinated chitosan (FCS) and therapeutic antibody-FCS are developed for synergistic immunotherapy against BCa. In this system, FCS is employed as a transepithelial carrier to assemble with bovine serum albumin (BSA)-flubendazole (FBZ) complex and anti-PD-1 (αPD-1) respectively, to facilitate efficient transepithelial delivery of intravesical FBZ-BSA and αPD-1 though transiently regulating the distribution of tight junction proteins on bladder epithelium. In addition, the FBZ–BSA complex exhibits tumor microenvironment-responsive charge reversal and BSA carrier-broken effects to drive tumor-targeted dissociation and drug release of FBZ–BSA/FCS. Moreover, FBZ not only promotes apoptosis and inhibits glycolysis in cancer cells but also displays adjuvant properties to activate potent immune responses through IL-12/IFN-γ pathway. Interestingly, combined perfusion of FBZ–BSA/FCS and αPD-1/FCS nano-formulations can significantly activate the tumor immune microenvironment, especially CD8 + T cell infiltration and αPD-1 sensitivity, and finally remarkably inhibit tumor growth in the mouse orthotopic BCa model. Thus, this study presents a novel intravesical delivery platform for ICB antibodies and a smart adjuvant system to achieve potent synergy immunotherapy, which is promising for bladder-preserving treatment against BCa.
研究领域:
药学
·
癌症研究
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免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yi Chen,Xian Shu,Jia-Yi Guo,Yun Xiang,Shi-Yu Liang,Jin-Mei Lai,Jia-Yi Zhou,Li-Han Liu,Ping Wang
As a potential treatment strategy for low immunogenic triple negative breast cancer (TNBC), photodynamic therapy (PDT) induced antitumor immunotherapy is greatly limited by the immunosuppressive tumor microenvironment (ITM), especially the M2 phenotype tumor-associated macrophages (TAMs). The balance of arginine metabolism plays an important role in TAMs polarization. Herein, a multifunctional nanoplatform (defined as HN-HFPA) was employed to burst the anti-tumor immunity of TNBC post PDT by reeducating TAMs through interfering the TAMs-associated arginine metabolism. The L -arginine ( L -Arg) was loaded in the hollow cavity of HN-HFPA, which could not only generate nitric oxide (NO) for tumor therapy, but also serve as a substrate of arginine metabolism pathway. As an inhibitor of arginases-1 (Arg-1) of M2 TAMs, L -norvaline ( L -Nor) was modified to the hyaluronic acid (HA), and coated in the surface of HFPA. After degradation of HA by hyaluronidase in tumor tissue and GSH-mediated disintegration, HN-HFPA depleted intracellular GSH, produced remarkable reactive oxygen species (ROS) under light irradiation and released L -Arg to generate NO, which induced tumor immunogenic cell death (ICD). Real-time ultrasound imaging of tumor was realized taking advantage of the gas feature of NO. The L -Nor suppressed the Arg-1 overexpressed in M2, which skewed the balance of arginine metabolism and reversed the ITM with increased ratios of M1 and CD8 + T cells , finally resulted in amplified antitumor immune response and apparent tumor metastasis inhibition . This study remodeled ITM to strengthen immune response post PDT, which provided a promising treatment strategy for TNBC.
研究领域:
癌症生物学
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免疫学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
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纳米技术
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免疫疗法
·
分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Jiang Tao,Tang Zixiang,Tian Shumiao,Tang Haitian,Jia Zhekun,Li Fangjian,Qiu Chenyue,Deng Lin,Ke Lang,He Pan,Liu Gang,Chu Chengchao,Xiong Yongfu
Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal–organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃] 2 ⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe 3 ⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe 3 ⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered 1 O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe 3 ⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal–ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies. Graphical
研究领域:
纳米医学
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癌症治疗
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生物无机化学
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生物医学工程
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免疫治疗
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
eLife
·
2024
·
IF 6.4
Youxi Liu,Meimei Yin,Xiaoting Mao,Shuai Wu,Shuangping Wei,Shujun Heng,Yichun Yang,Jinwen Huang,Zhuolin Guo,Chuan Li,Chao Ji,Liu Hu,Wenjie Liu,Ling-juan Zhang
Allergic contact dermatitis (ACD), a prevalent inflammatory skin disease, is elicited upon repeated skin contact with protein-reactive chemicals through a complex and poorly characterized cellular network between immune cells and skin resident cells. Here, single-cell transcriptomic analysis of the murine hapten-elicited model of ACD reveals that upon elicitation of ACD, infiltrated CD4+ or CD8+ lymphocytes were primarily the IFNγ-producing type 1 central memory phenotype. In contrast, type 2 cytokines (IL4 and IL13) were dominantly expressed by basophils, IL17A was primarily expressed by δγ T cells, and IL1β was identified as the primary cytokine expressed by activated neutrophils/monocytes and macrophages. Furthermore, analysis of skin resident cells identified a sub-cluster of dermal fibroblasts with preadipocyte signature as a prominent target for IFNγ+ lymphocytes and dermal source for key T cell chemokines CXCL9/10. IFNγ treatment shifted dermal fibroblasts from collagen-producing to CXCL9/10-producing, which promoted T cell polarization toward the type-1 phenotype through a CXCR3-dependent mechanism. Furthermore, targeted deletion of Ifngr1 in dermal fibroblasts in mice reduced Cxcl9/10 expression, dermal infiltration of CD8+ T cell, and alleviated ACD inflammation in mice. Finally, we showed that IFNγ+ CD8+ T cells and CXCL10-producing dermal fibroblasts co-enriched in the dermis of human ACD skin. Together, our results define the cell type-specific immune responses in ACD, and recognize an indispensable role of dermal fibroblasts in shaping the development of type-1 skin inflammation through the IFNGR-CXCR3 signaling circuit during ACD pathogenesis.
研究领域:
免疫学
·
皮肤病学
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转录组学
·
细胞生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Yi Chen,Qianming Du,Ying Zou,Qianqian Guo,Jing Huang,Ling Tao,Xiangchun Shen,Jianqing Peng
High metastasis is responsible for the failure in the treatment of melanoma . Chemoimmunotherapy has shown conspicuous inhibition effects not only on the growth of tumor in situ, but also on the metastasis to distant organs. Given that the indoleamine-2,3 dioxygenase (IDO) overexpressed in the microenvironment of tumor leads to the immune escape, the combination of chemotherapeutic drug and IDO inhibitor might be a promising chemoimmunotherapy. Besides, the hematogenous metastasis mediated by platelets was supposed to be blocked by the heparin (HP). Therefore, a drug delivery system with all these elements involved might be a potential treatment for melanoma. Here, we developed a pH-sensitive liposomal dual-delivery system for doxorubicin (DOX) and epacadostat (EPA) with HP coated (HP/LDE). It was confirmed to enhance cytotoxicity and apoptosis , reverse the platelets-activated epithelial mesenchymal transformation (EMT) and prevent the invasion and migration in vitro . After systemic administration , HP/LDE provided the optimum anti-metastasis effect on the melanoma. The results of evaluation on DC maturation, CD8 + cytotoxic T lymphocytes (CTLs) activation and T cell mediated cytotoxicity were consistent in vitro and in vivo . Taken together, our study established a functional liposomal dual-delivery system with ideal anti-metastasis efficacy on melanoma.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Feiyang Jin,Jing Qi,Minxia Zhu,Di Liu,Yuchan You,Gaofeng Shu,Yan Du,Jun Wang,Hui Yu,Mingchen Sun,Xiaoling Xu,Qiying Shen,Xiaoying Ying,Jiansong Ji,Yongzhong Du
A desirable cancer therapeutic strategy is supposed to have effective ability to not only exert maximum anticancer ability but also inspire antitumor immunity for preventing tumor relapse and metastasis. During this research, multifunctional upconversion nanoparticles (UCNPs) coated by ROS-responsive micelles are prepared for tumor targeting and near-infrared (NIR)-triggered photodynamic therapy (PDT)-combined synergistic effect of chemotherapy. Moreover, both PDT and chemotherapy agents could activate antitumor immunity via inducing immunogenic cell death with CD8+ and CD4+ T cells infiltrating in tumors. Through the experiments, intravenous administration of multifunctional nanocarriers with noninvasive NIR irradiation destroys the orthotopic tumors and efficiently suppresses lung metastasis in a metastatic triple-negative breast cancer model by cascade-amplifying chemo-PDT and systemic antitumor immunity. In conclusion, this study provides prospective chemo-PDT with inspired antitumor immunity for metastatic cancer treatment.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 21
·2101222
·
IF 9.933
Peng Yan,Yang Luo,Xinyang Li,Yingmin Li,Yi Wang,Jian Wu,Shaobing Zhou
In situ vaccination can trigger an antitumor immune response. However, the therapeutic effect is still limited since the high expression of adenosine binding to G protein-coupled receptor A2AR induces an immunosuppressive effect. In this work, a new formulation is presented with the combination of a nanovaccine based on redox-responsive polymer micelles and A2AR antagonist SCH58261. The micelles simultaneously encapsulate immunogenic cell death (ICD) inducer doxorubicin (DOX) and adjuvant toll-like receptor 7 and 8 (TLR7/8) agonist R848, acting as the potent in situ vaccines. A high concentration of glutathione in tumor cells leads to the disintegration of these micelles, releasing DOX and R848 to mediate ICD, inducing the activation of dendritic cells and initiating an immune response. Meanwhile, A2AR antagonist SCH58261, a generation immune checkpoint blocker, inhibits the immunosuppressive adenosinergic pathway in the tumor microenvironment, activating natural killer (NK) cells and CD8 + T cells, and inhibiting the proliferation of regulatory T cells. Therefore, this formulation can trigger a robust systemic antitumor immune response.
研究领域:
癌症研究
·
免疫学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2024
·
IF 4.2
Lisha Liu,Beiyuan Zhang,Xianggui Wu,Gang Cheng,Xiaopeng Han,Xiaofei Xin,Chao Qin,Lei Yang,Meirong Huo,Lifang Yin
Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.
研究领域:
肿瘤学
·
纳米技术
·
免疫疗法
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Weichong He,Wei Lv,Linfeng Liu,Yue Gong,Kefan Song,Jiangna Xu,Wei Zhao,Shengnan Li,Zhiyi Min,Qinhua Chen,Jiaqing Yin,Yuqin Chen,Hufeng Fang,Hongliang Xin,Xiangming Fang
Glioblastoma, the most prevalent malignant brain tumor, is a lethal threat to human health, with aggressive and infiltrative growth characteristics that compromise the clinical treatment. Herein, we developed a vitamin D3-inserted lipid hybrid neutrophil membrane biomimetic multimodal nanoplatform (designated as NED@MnO2-DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO2) which were coated with a vitamin D3-inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO2-DOX exhibited great power to activate and amplify immune responses related to the cGAS STING pathway, bolstering the secretion of type I interferon-β and proinflammatory cytokines, promoting the maturation of DC cells and infiltration of CD8+T cells into the glioma tissue, thereby reversing the immunosuppressive microenvironment of glioma from a “cold” tumor to a “hot” tumor. The biomimetic multimodal nanoplatform has potential as a multimodal strategy for glioma-targeted treatment, especially holding considerable promise for the development of innate immune therapy for glioma.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Heying Chen,Xiaomeng Cai,Jiayu Zhang,Hongyan Sun,Jie Zhang,Jun Chen,Zhenglin Yang,Dongqing Wang
Combination of chemotherapy and cancer immunotherapy has shown substantial clinical promise. However, the immunosuppressive tumor microenvironment (TME) poses a critical barrier to this combination therapy. Here, a tumor lysosome-targeted immunomodulatory strategy based on a biomimetic nanoadjuvant is presented, which effectively overcomes the immunosuppressive TME and demonstrates enhanced therapeutic efficacy when combined with chemotherapy. This nanoadjuvant integrates Fe-DOX coordination nanoparticles, a MnCO 3 shell, TLR7/8 agonist (R848), and a mature dendritic cell membrane (DCM) coating. The resulting DCM@(Fe-DOX-Mn-R848) nanoadjuvant induces immunogenic cell death in tumor cells via lysosomal-mitochondrial cascade destruction. Concurrently, it activates the cGAS-STING signaling pathway to promote dendritic cell maturation and repolarize tumor-associated macrophages from M2 to M1 phenotype, thereby effectively enhancing CD8 + T cell activation and tumor therapeutic efficacy. When combined with PD-L1 blockade therapy, the nanoadjuvant demonstrates enhanced efficacy in murine models of primary and recurrent triple-negative breast cancer, establishing durable immune memory. This platform demonstrates significant potential in overcoming immunosuppressive TME and advancing combination therapy through lysosome-targeting drug delivery technology, revealing promising prospects for cancer treatment.
研究领域:
纳米医学
·
免疫学
·
癌症生物学
·
生物工程
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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