Small
·
2024
·Vol. 20
·期 51
·2407038
·
IF 13
Xuefan Xiong,Ying Zhang,Xinqi Huang,Shusheng Zhang,Qiong Li
Photothermal therapy (PTT) against cancer not only directly ablates tumors but also induces tumor immunogenic cell death (ICD). However, the antitumor immune response elicited by ICD is insufficient to prevent relapse and metastasis because of the immunosuppressive tumor microenvironment (TME). A biomimetic nanoplatform (bmNP) mimicking cytotoxic lymphocytes (CTLs) for combinational photothermal-immunotherapy to effectively regulate the immunosuppressive TME is reported here. The bmNP is constructed by wrapping the T -cell membrane onto a new type of photothermal agents, spherical Au-based PNCs (sAuPNCs). Similar to T -cells, the bmNP enhanced accumulation at the tumor site by targeting the tumor via adhesion proteins on T -cell membrane. The obtained sAuPNCs have a wide absorption band in the second near-infrared (NIR-II) region with a high photothermal conversion efficiency (PCE) up to about 75% and excellent photostability. The bmNP with a smaller size is more superior compete with T -cells to bond with tumor cells via PD-1/PD-L1 interaction to effectively block the PD-1 checkpoint of T -cells for preventing T -cell exhaustion. Furthermore, in vivo studies reveal the immunological memory effect is significantly elicited in mice received bmNPs therapy. Collectively, bmNPs show great potential in photothermal-enhanced immunotherapy.
研究领域:
肿瘤学
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免疫学
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纳米医学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF CANCER
·
2025
·
IF 6.8
Yu Huijuan,Jin Shaowen,Zeng Min,Yang Zhiqing,Wang Xiaofei
Background T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) is a checkpoint receptor thought to be involved in mediating T-cell exhaustion and dysfunction of natural killer (NK) cells in tumours and is emerging as novel promising targets in immunotherapy, however, the ligand binding and the efficacy of its antibody still need to be further explored. Methods Four different TIGIT antibodies in characteristics of antigen binding, in vitro effects on activated T cells, Fc region functions and tumour inhibition in animal models were compared. The antibody as monotherapy and combined with anti-PD-L1 antibody, effects on PBMC in ex vivo coculture with autologous human CRC organoids as well as PK profile were evaluated. Results Studies demonstrated that TIGIT antibody with PVR-competitive ability as monotherapy resulted in inhibition of tumour growth, sustained anti-tumour immune memory in tumour re-challenge mice, enhanced anti-tumour therapy in combination with anti-PD-L1. Ex vivo coculture assay suggested that TIGIT antibody treatment activated immune cells and promoted infiltration and tumour killing ability of autologous PBMC in human CRC organoids. Conclusions Our study broadens the knowledge of TIGIT antibody in cancer immunotherapy and may benefit future development of next-generation checkpoint inhibitors with improved clinical outcomes.
研究领域:
肿瘤免疫学
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分子生物学
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药物研发
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Qinglian Hu,Xiaoyu Huang,Tong Wang,Zhuoting Lu,Dongchang Sun,Yuanxiang Jin
Bioengineered probiotics enable new opportunities to address abnormal cancer metabolism and suppressive immune–environment interactions for improved therapeutic susceptibility. Here, Escherichia coli Nissle 1917 (EcN) was constructed to convert ammonia into l-arginine continuously and was further modified with polydopamine (PDA) to form living biotherapeutic argEcN@P for enhanced colorectal cancer eradication. Benefiting from the movement of EcN, argEcN@P could colonize and penetrate deep in tumors through hypoxia targeting and increase the intratumoral l-arginine concentrations. Upon near-infrared light (NIR) irradiation, heating induced by PDA could ablate tumor cells efficiently and release tumor antigens, which induce immunogenic cell death (ICD). More interestingly, argEcN@P remarkably promotes differentiation into M1-like macrophages in tumor tissues, inhibiting primary, distant tumor growth by inducing potent adaptive antitumor immunity. More importantly, argEcN@P treatment efficiently prevented postoperative tumor recurrence by inducing long-term immune memory. Taken together, this platform based on bioengineered probiotics provides a promising strategy for tumor metabolic reprogramming sensitized photothermal immunotherapy in deep tumors.
研究领域:
肿瘤学
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微生物学
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免疫学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Chenyao Qian,Huan Wang,Jinyue Bi,Xiaodan Zheng,Rujia Li,Huan Luo,Xueyong Qi,Song Shen,Jin Cao
Cutaneous melanoma is characterized by malignant proliferation, high aggressiveness, high metastasis, rapid recurrence, and low survival rate; therefore, research on its treatment is vital. In this study, a novel nano system combining sonodynamics and immunotherapy for cutaneous melanoma treatment was designed and developed. Based on the use of phycocyanin for the biomineralization of manganese ions, smart and multifunctional manganese phycocyanin nanoparticles encapsulating the immune adjuvant levamisole (LMS) with melanoma B16-OVA cell membranes wrapped around its outer layer (Mn-PCNP-LMS@CM) were designed and prepared. The experimental results showed that Mn-PCNP-LMS@CM efficiently targeted cutaneous melanomas. Under ultrasonic excitation, it catalyzed oxygen production from hydrogen peroxide in the tumor environment, reduced high glutathione levels in tumor tissues, and significantly enhanced (reactive oxygen species) ROS generation, thus improving the outcome of sonodynamic therapy. In contrast, sonodynamic therapy induced immunogenic death of tumor cells, together with the loaded immune adjuvant levamisole, which promoted the maturation of dendritic cells (DCs), modulated the immunosuppressive microenvironment, enhanced the immunotherapeutic effect, and stimulated the function of long-term immune memory to prevent tumor growth and recurrence. This study is expected to provide new ideas for developing novel anti-tumor nano systems and achieving anti-tumor synergistic therapy.
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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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Xuemeng Guo,Xiang Li,Sijie Wang,Yingying Shi,Jiaxin Huang,Xu Liu,Yichao Lu,Junlei Zhang,Lihua Luo,Jian You
Adoptive cell therapy (ACT) emerged as a promising approach for cancer treatment, yet its application in solid tumors faced challenges such as inadequate tumor infiltration and cellular dysfunction. Histone acetylation is reported to play a crucial role in restoring T-cell function within tumor tissues. Building upon previous research, a novel strategy involving the co-loading of two drugs, G3C12 and vorinostat (SAHA), into PLGA microspheres to form G3C12+SAHA@PLGA is developed for intratumoral injection. The G3C12 peptide enhances adoptive T-cell recruitment to the tumor site by modulating the binding state of IFN-γ. While SAHA, a histone deacetylase inhibitor, promotes memory phenotypes of infiltrating T-cells and prevents their transition to an exhausted state. This synergistic approach effectively augmentes the efficacy of ACT in the “cold” tumor model (4T1) or the “hot” tumor model (CT26). These findings highlight the potential of combining epigenetic regulation with recruitment signaling as a means to enhance the therapeutic impact of ACT in treating solid tumors.
研究领域:
肿瘤免疫学
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表观遗传学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Yangning Lan,Xiaoxuan Zhang,Shaorui Liu,Chen Guo,Yuxiao Jin,Hui Li,Linyixiao Wang,Jinghong Zhao,Yilin Hao,Zhicheng Li,Zhaoyuan Liu,Florent Ginhoux,Qi Xie,Heping Xu,Jie-Min Jia,Danyang He
Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1（Spp1） to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1 + microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.
研究领域:
神经科学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
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IF 8.947
Xuan Zhang,Yan Zhang,Haiping Zheng,Yufeng He,Honglin Jia,Liyuan Zhang,Chunjie Lin,Shuang Chen,Junfeng Zheng,Qunfang Yang,Tao Liu,Xichun Pan,Haigang Zhang,Chenhui Wang,Lei Ren,Wenjun Shan
Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8 + T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. Statement of significance Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property , and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields.
研究领域:
肿瘤学
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免疫学
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纳米医学
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生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yue Yin,Lu Tang,Yuqi Cao,Hening Liu,Cong Fu,Jingwen Feng,Houhua Zhu,Wei Wang
The metastasis and recurrence of cancer post-surgery remain the major reasons for treatment failures. Herein, a photo-immune nanoparticle decorating with M1 macrophage membrane (BD@LM) is designed based on the inflammatory environment after surgical resection. By loading photosensitizer black phosphorus quantum dots (BPQDs) and chemotherapeutics doxorubicin (DOX) in BD@LM nanoparticles, an effective chemophototherapy-mediated immunogenic cell death of tumor cells is triggered, subsequently leading to the maturation of dendritic cells for further immune cascade. Moreover, by accommodating BD@LM in a dissolvable microneedle patch, the skin barrier is directly broken for efficacious delivery of BD@LM into solid tumors, which boosts the effectiveness of aPD-L1-based checkpoint blockade therapy. Consequently, the growth of both orthotopic and post-surgical breast tumor and melanoma is significantly inhibited. Specifically, an effective T cell activation accompanied with dramatic inhibition of immunosuppressive cells is observed. Meanwhile, the proportion of memory T cells remarkably grows after proposed treatment, indicating the establishment of a long-term immune memory effect for prevention of second tumor attack. Altogether, this work offers a meaningful strategy by combining photo-immune-inspired nanoparticles with microneedle patches for boosting aPD-L1-based tumor immunotherapy.
研究领域:
肿瘤学
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免疫学
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纳米医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 26
·6147-6158
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IF 7
Xiaoxi Song,Chun Zhang,Mengyuan Xing,Chunyan He,Dongxu Wang,Lijuan Chong,Xiuli Zhang,Minghui Chen,Jingjing Li
Photothermal therapy (PTT) is an effective and well-documented approach to thermally ablate tumors. However, the side effect of distal metastasis and recurrence limit its further expansion. At the same time as PTT was developed, the employment of imaging to monitor the treatment of tumors also became meaningful. Herein, as a proof of concept, gadolinium-doped mesoporous carbon nanoparticles (Gd-MCNs) were prepared as nanocarriers, MRI contrast agents, and PTT agents by a one-step hard template method, which realized Gd doping and carbon filling simultaneously, while retaining enough pore space for drug loading. After loading the immune adjuvant, R837, and the coating of tumor extracellular vesicle, the obtained biomimetic nanoparticles (EV@Gd-MCNs-R837) not only allowed tumor MRI, but also inhibited the primary tumor and its metastasis with long-term immune memory in vivo. This study provides proof for the potential of Gd-MCNs-based biomimetic nanoparticles for targeted PTT/immune-enhanced synergistic theranostic of tumors.
研究领域:
纳米技术
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生物医学工程
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癌症治疗
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分子影像
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
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IF 14
Ping Huang,Yao Yang,Wenyan Wang,Zimu Li,Nansha Gao,Hongzhong Chen,Xiaowei Zeng
Insufficient immune stimulation and stubborn immune resistance are the critical factors limiting tumor immunotherapy. Here, we report a multifunctional nanoprodrug platform with self-driven indoximod (IND) release and oxidative stress amplification. The aim is to awaken immune responses and block the indoleamine 2,3-dioxygenase (IDO) pathway through a combination of ferroptosis , photothermal therapy, and immunotherapy. This nanosystem improved the delivery efficiency of IND due to click chemistry linked ROS responsive prodrug and self-driven drug release. Meanwhile, the tactic of simultaneously increasing ROS and eliminating GSH amplified oxidative stress and strengthened ferroptosis, which further enhanced immunogenicity along with polydopamine-based photothermal therapy. IDO immunization combined with ferroptosis as well as photothermal therapy not only stimulated immune response, but also reversed immune suppression with enhanced immune memory . Therefore, primary tumor, distant tumor, and cancer metastasis were inhibited. This study provides a perspective on immunotherapeutics for cancer treatment.
研究领域:
癌症治疗
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纳米医学
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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
Aggregate
·
2024
·
IF 13.9
Aihui Wang,Liqun Li,Liqian Zheng,Bang-Ping Jiang,Yihao Liu,Rimei Huang,Huimin Qiu,Shichen Ji,Hong Liang,Xing-Can Shen
Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme-nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme-based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three-dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near-infrared light-mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug-resistant bacteria by the skeleton modification with genipin to produce genipin-conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO 4 -crosslinked GLZF hydrogel is constructed to sensitize the cGAS-STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti-recurrence of diabetic wound infection via photo-enhanced bacterial killing and the cGAS-STING pathway. Thereby, it paves the way to employ the universal divalent anion-mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.
研究领域:
材料科学
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生物材料
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生物医学工程
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免疫学
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伤口愈合
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产品关联
DOI
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 42
·19912-19922
·
IF 6.97
Dongsheng Zhang,Ping Cui,Zhichao Dai,Baochan Yang,Xiuxiu Yao,Qingyun Liu,Zunfu Hu,Xiuwen Zheng
The metastasis and recurrence of tumors are the main reasons for cancer death. In this work, a promising therapy for tumor treatment that can eliminate primary tumors and prevent tumor relapses is introduced by combining chemotherapy, photothermal therapy (PTT) and immunotherapy. Multifunctional FePt/MoS2-FA nanocomposites (FPMF NCs) were obtained via anchoring FePt nanoparticles and folic acid (FA) on MoS2 nanosheets. As an efficient ferroptosis agent, FePt nanoparticles could catalyze the Fenton reaction to produce the reactive oxygen species (ROS). Through the highly effective photothermal conversion of MoS2 nanosheets, the primary tumor cells could be ablated by photothermal therapy (PTT). Moreover, the metastatic tumors were eliminated effectively with the help of oligodeoxynucleotides containing cytosine–guanine (CpG ODNs) combined with systemic checkpoint blockade therapy using an anti-CTLA4 antibody. Even more intriguingly, a strong immunological memory effect was obtained by this synergistic therapy. Taking all these results into consideration, we anticipate that the photo-chemo-immunotherapy strategies show great promise toward the development of a multifunctional platform for anticancer therapeutic applications.
研究领域:
肿瘤学
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纳米技术
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免疫疗法
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材料科学
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治疗学
✓ 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）