Pharmaceutics
·
2023
·Vol. 15
·期 4
·1309
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IF 5.4
Yanlin Feng,Yumei Xu,Zhaoyang Wen,Xin Ning,Jianlin Wang,Deping Wang,Jimin Cao,Xin Zhou
Background: Triple-negative breast cancer (TNBC) was closely related to high metastatic risk and mortality and has not yet found a targeted receptor for targeted therapy. Cancer immunotherapy, especially photoimmunotherapy, shows promising potential in TNBC treatment because of great spatiotemporal controllability and non-trauma. However, the therapeutic effectiveness was limited by insufficient tumor antigen generation and the immunosuppressive microenvironment. Methods: We report on the design of cerium oxide (CeO2) end-deposited gold nanorods (CEG) to achieve excellent near-infrared photoimmunotherapy. CEG was synthesized through hydrolyzing of ceria precursor (cerium acetate, Ce(AC)3) on the surface of Au nanorods (NRs) for cancer therapy. The therapeutic response was first verified in murine mammary carcinoma (4T1) cells and then monitored by analysis of the anti-tumor effect in xenograft mouse models. Results: Under near-infrared (NIR) light irradiation, CEG can efficiently generate hot electrons and avoid hot-electron recombination to release heat and form reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and activating part of the immune response. Simultaneously, combining with PD-1 antibody could further enhance cytotoxic T lymphocyte infiltration. Conclusions: Compared with CBG NRs, CEG NRs showed strong photothermal and photodynamic effects to destroy tumors and activate a part of the immune response. Combining with PD-1 antibody could reverse the immunosuppressive microenvironment and thoroughly activate the immune response. This platform demonstrates the superiority of combination therapy of photoimmunotherapy and PD-1 blockade in TNBC therapy.Keywords:cerium end-deposited gold nanorods;photoimmunotherapy;PD-1 blockade;triple-negative breast cancer
研究领域:
纳米技术
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癌症治疗
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免疫学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2025
·
IF 5.9
Dong-Ni Pei,Yang Song,Ying-Xia Zhou,Bo Shu,Shao-wei Huang,Fa-Zhao Li,Wei-Dong Dai,Bao-Ye Sun
Purpose Conventional type 1 dendritic cells (cDC1s) mastermind anti-cancer immunity and play a pivotal role in determining the efficacy of cancer immunotherapies. In this study, we sought to decipher the dynamic changes in the tumor immune landscape during intrahepatic cholangiocarcinoma (iCCA) development and harness the therapeutic potential of targeting cDC1s for cancer therapy. Methods We constructed spontaneous murine iCCAs via hydrodynamic tail vein injection (HDTVi) of plasmids encoding AKT/YAP. To characterize tumor-infiltrating immune cell populations throughout iCCA carcinogenesis and progression, we performed time-of-flight mass cytometry (CyTOF). To expand and activate cDC1s, we combined Flt3L with poly I:C (FL-pIC) therapy and assessed its therapeutic efficacy in both AKT/YAP-induced iCCAs and a subcutaneous tumor injection model. Flow cytometric analyses were used to evaluate intra-tumoral infiltration levels of cDCs and CD8 + T cells. Results CyTOF analysis revealed the progressive formation of an immunosuppressive tumor microenvironment as iCCA advances. Crucially, infiltration of cDC1s dramatically decreases in advanced iCCAs compared to early-stage tumors. Combined FL-pIC therapy preferentially expanded CD103 + cDC1s, powerfully inhibiting tumorigenesis in AKT/YAP-driven murine iCCAs and sensitizing these tumors to anti-PD-1 therapy. Moreover, FL-pIC therapy markedly suppressed the growth of established mIC-23 subcutaneous tumors. Conclusions Our findings demonstrate that recruiting and activating intra-tumoral cDC1s is feasible and essential for driving anti-tumor CD8 + T cell immune responses and enhancing anti-PD-1 therapeutic effectiveness in iCCA.
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jia Yao,Pengtao Chen,Dingqi Xie,Jianqingchen Chen,Xiao Lin,Yujin Xu
Radiotherapy (RT) is a widely used clinical treatment for cancer, leveraging ionizing radiation; however, some patients exhibit resistance to radiation due to insufficient reactive oxygen species (ROS) production. Copper-based nanomaterials represent a promising class of antitumor agents capable of generating abundant ROS. In this study, R837 and Cu2–xSe were incorporated into PLGA (50:50)20k-PEG2k-iRGD to develop a targeted nanomaterial for tumor therapy. These nanoparticles effectively induced cuproptosis, inhibited tumor cell proliferation, remodeled the tumor immune microenvironment (TME), and promoted immunogenic cell death (ICD), thereby enhancing the efficacy of PD-1 checkpoint blockade therapy (αPD-1). Furthermore, our results demonstrated that the Cu2–xSe(R837)-iRGD nanoformulations, in combination with radiotherapy, promoted the infiltration of CD8+ T cells and activated antitumor immune responses in vivo. In conclusion, our study confirmed that Cu2–xSe(R837)-iRGD nanoformulations combined with radiotherapy yielded promising therapeutic outcomes and held potential for clinical application in osteosarcoma (OS) treatment.
研究领域:
肿瘤学
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纳米医学
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免疫治疗
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辐射生物学
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生物无机化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2024
·Vol. 52
·期 4
·1-8
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IF 3.8
Tong Wang,Xu Ye,Hao Jiang,Yu Gao
B‑cell lymphoma is difficult to cure because of its biological and clinical heterogeneity, and due to native chemoresistance. Immunotherapies that overcome cancer‑induced immune evasion have been the center of recent developments in oncology. This is emphasized by the accomplishment of various agents that disrupt programmed cell death protein 1 (PD‑1)‑mediated immune suppression in diverse tumors. However, while PD‑1 blockade has been effective in numerous malignancies, a significant proportion of cancers, including B‑cell lymphoma, show certain rates of primary resistance to these therapeutic strategies. Histone deacetylase inhibitors (HDACis) have exhibited anticancer activity though suppressing cell proliferation, inducing differentiation and triggering apoptosis. The present study aimed to explore a therapeutic strategy combining a HDACi (romidepsin) and PD‑1 blockade (BMS‑1) in B‑cell lymphoma, utilizing a constructed mouse model of B‑cell lymphoma. The IC50 of the two inhibitors was confirmed by MTT assay, and their inhibitory effects were revealed to be dose‑ and time‑dependent. The data demonstrated that the combined treatment of romidepsin and BMS‑1 synergistically inhibited the growth of B‑cell lymphoma. Furthermore, it was revealed that romidepsin and BMS‑1 synergistically triggered apoptosis in mouse B‑cell lymphoma. The synergistic effect of these agents was capable of activating tumor‑infiltrating lymphocytes, particularly CD3+CD4+ and CD3+CD8+ T cells. The results of the present study underscore the potential of HDAC inhibition in conjunction with PD‑1 blockade as a novel therapeutic approach for B‑cell lymphoma, highlighting the synergistic effects of these two mechanisms in enhancing antitumor immunity.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Linlin Song,Zhihui Liu,Xiujing He,Tianyue Xu,Meixu Chen,Zihan Xu,Haina Zhao,Jiaojiao Suo,Hong Wang,Zhankun Yang,Shenglan You,Xiaoting Chen,Guang Yang,Jing Jing,Yulan Peng,Hubing Shi
Synchronizing therapy and diagnosis is an ideal mode for clinical treatment of localized disease, e.g., tumor. Here, we develop a diagnosis-therapy coupled sonodynamic nano delivery system ZSMT which is constructed with a TiO 2 embedding hollow Mn-MOF. Loaded with perfluorohexane, the ZSMT nanoparticle is not only capable for carrying ozone as a ROS donor but also endowed with double modes of imaging, namely ultrasound and magnetic resonance imaging. The TiO 2 -Mn-MOF can efficiently generate ROS by sonodynamic catalyzing ozone. Moreover, fluorescent tracer indicates the ZSMT particle can be internalized by tumor cells. With the stimulation of ultrasound, ozone carried ZSMT potently inhibits cell proliferation and promotes immunogenic cell death in vitro and in vivo by inducing a mitochondrial related cell death. Remarkably, combination of ultrasound-responsive ozone catalytic nano system and PD-1 blockade systematically suppresses the tumor growth by reprogramming the immune microenvironment. In conclusion, our sonodynamic nano system not only proves the principle of drug administration strategy on “treat-as-you-see” but also provides a combo regimen of improving PD-1 blockade with precision localized antigen boosting.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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医学影像
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癌症生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 27
·2202744
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IF 17.521
Songtao Dong,Yuan Zhang,Xiangnan Guo,Chuang Zhang,Zhaomeng Wang,Jiang Yu,Yubo Liu,Chang Li,Yuting Hu,Bingjun Sun,Mengchi Sun,Haotian Zhang,Defang Ouyang,Zhonggui He,Yongjun Wang
Spatiotemporal delivery of nanoparticles (NPs) at the “cellular level” is critical for nanomedicine, which is expected to deliver as much cytotoxic drug into cancer cells as possible when NPs accumulate in tumors. However, macrophages and cancer-associated fibroblasts (CAFs) that are present within tumors limit the efficiency of spatiotemporal delivery. To overcome this limitation, glutathion pulse therapy is designed to promote reduction-sensitive Larotaxel (LTX) prodrug NPs to escape the phagocytosis of macrophages and penetrate through the stromal barrier established by CAFs in the murine triple negative breast cancer model. This therapy improves the penetration of NPs in tumor tissues as well as the accumulation of LTX in cancer cells, and remodels the immunosuppressive microenvironment to synergize PD-1 blockade therapy. More importantly, a method is established that can directly observe the biodistribution of NPs between different cells in vivo to accurately quantify the target drugs accumulated in these cells, thereby advancing the spatiotemporal delivery research of NPs at the “cellular level.”
研究领域:
纳米医学
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癌症治疗
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免疫疗法
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2022
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IF 14.903
Tong Gao,Xiao Sang,Xinyan Huang,Panpan Gu,Jie Liu,Yongjun Liu,Na Zhang
Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.
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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纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-15
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IF 10.2
Su Runping,Gu Jingjing,Sun Juanjuan,Zang Jie,Zhao Yuge,Zhang Tingting,Chen Yingna,Chong Gaowei,Yin Weimin,Zheng Xiao,Liu Bingbing,Huang Li,Ruan Shuangrong,Dong Haiqing,Li Yan,Li Yongyong
Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of “antigen multi-copy display” and “calcium carbonate (CaCO 3 ) biomineralization” to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO 3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4 + T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO 3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.
研究领域:
癌症免疫疗法
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纳米技术
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Bowen Dai,Haoyu Yu,Tao Zhang,Kun Wang,Wei Xiong,Zhaojian Gong,Tianhan Kai
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis and limited treatment options. To address the challenges of conventional therapy resistance, antioxidant defence, and immune evasion, we developed a multifunctional nanozyme platform, MIL-100(Fe)@Pt@R837@HA (HMPR), that integrates electrodynamic therapy (EDT), chemodynamic therapy, and immunotherapy. The multi-enzyme activities of HMPR allow for the oxygen generation, hydroxyl radicals production, and glutathione depletion, thereby alleviating hypoxia and triggering both apoptosis and ferroptosis. Under electrical stimulation, HMPR promotes significant production of reactive oxygen species via Pt-mediated EDT to amplify ferroptosis and immunogenic cell death (ICD). In addition, the tumor-specific GSH level triggers the release of the immune adjuvant R837. The potent ICD effect, combined with the sustained release of the adjuvant R837, endows the nanozyme HMPR with the characteristics of an in situ “tumor vaccine”, continuously promoting dendritic cell maturation, activating T cell-mediated immunity, and establishing long-term immunological memory to prevent tumor recurrence and inhibition of distant tumor growth. This cascade effect reprograms the immunosuppressive tumor microenvironment into an immunostimulatory one, significantly enhancing the efficacy of PD-1 blockade. Our study provides a powerful electro-enhanced nanozyme-immune synergistic strategy for OSCC and offers a flexible platform adaptable to other solid tumors.
研究领域:
肿瘤学
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纳米医学
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免疫治疗
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生物工程
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活性氧生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Linlin Song,Dan Zheng,Jinshun Xu,Tianyue Xu,Zhihui Liu,Huan Zhang,Yi Li,Yulan Peng,Hubing Shi
Despite revolutionary achievements have been made in clinical cancer therapy, the immune checkpoint blockade regimen still presents limited efficacy on tumors lack of neoantigens exposure. Here, we designed and synthesized an on-demand microwave-controlled ozone release nanosystem to specifically generate reactive oxygen species in tumor mass. By taking advantage of iRGD modification, the synthesized nanosystem can be specifically enriched in the tumor microenvironment and subsequently internalized by tumor cells. Triggered by the low-power microwave, ozone was released from the nanocarriers and inhibited tumor cell growth in vitro and in vivo . Molecular mechanism investigation further unraveled that the released-ozone induced cytolytic cell death through the rapid generation of reactive oxygen species such as hydroxyl radical. The tumor-specific neoantigen derived from this immunogenic cell death promoted cytotoxic T-lymphocytes infiltration, which provided a fundament for immune checkpoint blockade therapy. In the triple-negative breast cancer animal model, tumor-specific delivery of ozone significantly improved the systematical anti-tumor efficacy of the PD-1 blockade antibody. Notably, tumor-locally confined microwave-controlled release avoided systematic toxicity in the tested animals. Collectively, our nanosystem provides a novel controllable strategy for promoting immune checkpoint blockade therapy, especially in tumor types deficient in infiltrated T-lymphocytes.
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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肿瘤学
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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 COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4 + and CD8 + T cells . Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment.
研究领域:
肿瘤学
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纳米技术
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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
DOI
PubMed
高影响因子
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