Materials Today Bio
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2026
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IF 11
Hui Zhang,Xu Zhu,Jingchun Wang,Yibo Huo,Yikai Ma,Shengzhong Rong,Yuting Lu,Yingxue Jin
To address the core issue of low clinical response rates (10%-30%) to α-PD-L1 immune checkpoint blockade therapy, this study targeted the immunosuppressive bottleneck mediated by lactate accumulation in the tumor microenvironment (TME). A targeted drug delivery system (HLC) was constructed using hyaluronic acid (HA) nanomicelles co-loaded with lactate oxidase (LOX) and copper-doped carbon dots (CuCDs). Combined with α-PD-L1, a synergistic antitumor strategy integrating lactate metabolic regulation, cuproptosis, and immune activation was established. HLC achieves targeted accumulation through specific binding between HA and CD44 receptors on tumor cells. It directionally releases LOX and CuCDs in the acidic TME via pH-responsive properties. LOX efficiently clears lactate and elevates pH, blocking the HIF-1α/PD-L1 pathway to reverse immunosuppression. It also generates H 2 O 2 in situ to provide substrates for Cu-mediated Fenton-like reactions, enhancing cuproptosis. In vitro experiments confirm that HLC promotes dendritic cell maturation and drives M2-type macrophage polarization toward the M1 phenotype. In vivo studies using CT26 tumor-bearing mouse models show that HLC combined with 808 nm laser and α-PD-L1 significantly inhibits primary and distant tumor growth. It remodels the antitumor immune microenvironment with favorable biosafety. This study elucidates the synergistic mechanism between lactate metabolic regulation and cuproptosis, establishes an association between lactate level and cuproptosis sensitivity, and provides a novel strategy and experimental basis for combined cancer immunotherapy with important clinical translation value.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Lianghui Zhan,Qian Liu,Changjun Zhang,Jinbao Pu,Ligang Ren
Ethnopharmacological relevance Hedysarum polybotrys Hand.-Mazz. (Hongqi, HQ) is a prized Qi-tonifying herb in Traditional Chinese Medicine (TCM), historically employed to enhance the body's resistance and modulate immune function. While its anti-tumor properties are recognized, the specific immunomodulatory mechanisms by which HQ empowers Natural Killer (NK) cells to combat prostate cancer (PCa) remain under-explored. Aim of the study To systematically elucidate the material basis and molecular mechanisms through which the aqueous extract of HQ enhances NK cell-mediated cytotoxicity against PCa cells, utilizing an integrated approach of multi-omics and experimental validation. Methods The chemical profile of HQ aqueous extract was characterized using UHPLC-MS/MS untargeted metabolomics. Network pharmacology and transcriptomic analyses (RNA-seq) were integrated to predict core targets and signaling pathways. Specific interactions were simulated via molecular docking. Validations were performed using an in vitro co-culture model of NK-92 and PC-3 cells. Assays included CCK-8, LDH release, flow cytometry (apoptosis, surface markers), ELISA (cytokines), and Western blot. Results A total of 69 compounds were identified in HQ, with Genistein and Isoliquiritigenin highlighted as key active constituents. HQ treatment significantly enhanced NK-92 cell cytotoxicity against PC-3 cells, evidenced by increased LDH release and PC-3 apoptosis. Mechanistically, HQ upregulated the expression of cytolytic effectors (Perforin, Granzyme B) and pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17A). Crucially, HQ treatment achieved a "dual-effect": it reactivated the PI3K/AKT signaling pathway in NK cells (confirmed by increased p-PI3K and p-AKT levels) while concurrently downregulating the immunosuppressive PD-1/PD-L1 checkpoint axis. Conclusion This study demonstrates that HQ potentiates NK cell anti-tumor immunity against prostate cancer through a dual mechanism involving PI3K/AKT pathway activation and PD-1/PD-L1 axis inhibition. These findings provide modern pharmacological evidence supporting the traditional use of HQ for enhancing immune surveillance in cancer therapy.
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高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 9
·3453-3464
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IF 6.843
Xiaofang Li,Wen Zhang,Jing Lin,Hao Wu,Yucen Yao,Jiayi Zhang,Chunrong Yang
The application of combination immune-chemotherapy makes up for the limitation of monotherapy and achieves superior antitumor activity against cancer. However, combinational therapy is always restricted by poor tumor targeted drug delivery efficacy. Herein, novel T cell membrane cloaking tumor microenvironment-responsive nanoparticles (PBA modified T cell membrane cloaking hyaluronic acid (HA)-disulfide bond-vitamin E succinate/curcumin, shortened as RCM@T) were developed. T cell membrane cloaking not only serves as a protection shell for sufficient drug delivery but also acts as a programmed cell death-1(PD-1) “antibody” to selectively bind the PD-L1 of tumor cells. When RCM@T is intravenously administrated into the blood stream, it accumulates at tumor sites and responds to an acidic pH to achieve a “membrane escape effect” and expose the HA residues of RCM for tumor targeted drug delivery. RCM accumulates in the cytoplasm via CD44 receptor mediated endocytosis and intracellularly releases antitumor drug in the intracellular redox microenvironment for tumor chemotherapy. T cell membrane debris targets the PD-L1of tumor cells for tumor immunotherapy, which not only directly kills tumor cells, but also improves the CD8+ T cell level and facilitates effector cytokine release. Taken together, the as-constructed RCM@T creates a new way for the rational design of a drug delivery system via the combination of stimuli-responsive drug release, chemotherapeutical agent delivery and cell membrane based immune checkpoint blockade immunotherapy.
研究领域:
肿瘤学
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药理学
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免疫疗法
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纳米技术
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药物递送系统
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高影响因子
Nano Today
·
2022
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IF 18.962
Hao Tian,Guohao Wang,Wei Sang,Lisi Xie,Zhan Zhang,Wenxi Li,Jie Yan,Ye Tian,Jie Li,Bei Li,Yunlu Dai
Dendritic cells (DCs) play a key role in the presentation of tumor antigens to initiate innate and adaptive immune responses. While the tumor microenvironment (TME) contains a network of immunosuppressive factors that inhibit the differentiation and maturation of DCs. Immunoadjuvants have been focusing on modulating DCs function to improve cancer immunotherapy . Herein, a phenolic nanoadjuvant was developed by self-assembly of the sonosensitizer polymer (PEG-b-IR), GSH inhibitor (sabutoclax), Mn 2+ and TME acidic sensitive phenolic polymer (PEG-b-Pho) via metal–phenolic coordination. The combinational action of SDT-mediated ICD effect and Mn 2+ promoted the activation of the cGAS-STING pathway significantly enhanced DCs maturation. Furthermore, this phenolic nanoadjuvant greatly sensitizes tumors to PD-L1 checkpoint blockade immunotherapy, resulting in efficiently inhibiting the growth of distant tumors and restraining lung metastasis. Therefore, our work provides the potential to remedy the therapeutic limitation of insufficient antitumor immunity for enhanced 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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治疗学
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高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2023
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IF 4.9
Hui Jiang,Yingying Zhou,Dongdong Zheng,Yexiazi Cheng,Dacheng Xiang,Lixin Jiang,Jing Du
Triple negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and it is difficult to progress through traditional chemotherapy. Therefore, the treatment of TNBC urgently requires agents with effective diagnostic and therapeutic capabilities. In this study, we obtained programmed death-ligand 1 (PD-L1) antibody conjugated gold nanoshelled poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) encapsulating doxorubicin (DOX) (DOX@PLGA@Au-PD-L1 NCs). PLGA NCs encapsulating DOX were prepared by a modified single-emulsion oil-in-water (O/W) solvent evaporation method, and gold nanoshells were formed on the surface by gold seed growth method, which were coupled with PD-L1 antibodies by carbodiimide method. The fabricated DOX@PLGA@Au-PD-L1 NCs exhibited promising contrast enhancement in vitro ultrasound imaging. Furthermore, DOX encapsulated in NCs displayed good pH-responsive and photo-triggered drug release properties. After irradiating 200 μg/mL NCs solution with a laser for 10 min, the solution temperature increased by nearly 23°C, indicating that the NCs had good photothermal conversion ability. The targeting experiments confirmed that the NCs had specific target binding ability to TNBC cells overexpressing PD-L1 molecules. Cell experiments exhibited that the agent significantly reduced the survival rate of TNBC cells through photochemotherapy combination therapy. As a multifunctional diagnostic agent, DOX@PLGA@Au-PD-L1 NCs could be used for ultrasound targeted contrast imaging and photochemotherapy combination therapy of TNBC cells, providing a promising idea for early diagnosis and treatment of TNBC.
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JOURNAL OF ORAL PATHOLOGY & MEDICINE
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2021
·Vol. 51
·期 1
·74-85
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IF 4.253
Jing-Ya Yang,Fang Wang,Gang Zhou
Background Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP. Methods Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation. Results Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4 + , CD69 + , CD103 + and PD-1 + MAIT cells was increased in OLP, while that of CD8 + and CD49d + MAIT cells was decreased. The percentage of CD103 + , PD-1 + and PD-L1 + γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity. Conclusion The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role in the pathogenesis of OLP.
研究领域:
免疫学
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炎症
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口腔疾病
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细胞生物学
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PubMed
高影响因子
BIOMATERIALS
·
2022
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IF 15.304
Wenfei Chen,Chunting He,Nan Qiao,Zhaofei Guo,Shilong Hu,Yuanshuai Song,Hairui Wang,Zhirong Zhang,Bowen Ke,Xun Sun
Intratumoral environment as a hypoxic, non-inflamed “cold” state is difficult for many agents to accumulate and activate the immune system. Intrinsically, facultative anaerobic Salmonella VNP20009 target the tumor hypoxic areas, invade into tumor cells and exhibit an immune effect. Here we engineer the bacteria by decorating their surface with newly synthesized heptamethine cyanine dyes NHS–N782 and JQ-1 derivatives to obtain the biohybrid agent N –V-J, leading to the deep tumor targeted photothermal therapy and magnified immunotherapy. Due to the mitochondrial targeting capacity of NHS–N782, N –V-J becomes susceptive to the temperature rise when reaching tumors. This synergistic strategy promotes the systemic immunity by creating an inflamed “hot” tumor state from three different dimensions, which include the inherent immunogenicity of bacteria, the near-infrared laser triggered tumor antigens and the downregulation of PD-L1 expression. All these approaches result in effective and long-lasting T cell immune responses to prevent local and distant tumors for extended time. Leveraging the attenuated bacteria to transport dual drugs to the tumor tissues for self-synthetic vaccines provides a novel paradigm to enhance the bacteria-mediated cancer immunotherapy .
研究领域:
癌症生物学
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免疫学
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治疗学
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Caiting Meng,Chenyang Qiao,Qian Hao,Jiahong Shi,Chunju Lou,Jiaqi Song,Leyan Wang,Jinfan Yang,Xiaobin Ma,Huafeng Kang,Hao Wu,Zhengquan Yu,Shuaijun Li
The combination of radiotherapy and immune checkpoint blockade (ICB) therapy has demonstrated considerable efficacy in oncological treatment. However, the clinical PD-L1 antibody (anti-PD-L1) for glioblastoma (GBM) imprecisely accumulated in intracranial radiotherapy target and is often compromised by the formidable blood-brain barrier (BBB). To address these challenges, the study innovatively engineers a hierarchical precision delivery nanoplatform (FB-aPD-L1). This nanoplatform leverages sulfated fucoidan, which exhibited targeted affinity for P-selectin, an adhesion molecule expressed with spatiotemporally restricted specificity in response to radiotherapy. Following precise capture FB-aPD-L1 and crossing BBB, there is ultrasensitive release of BPA 4 -aPD-L1 and fucoidan in the tumor microenvironment. The targeted conjugation of 5-borono-2-pyridinecarboxylic acid (BPA) and sialic acid (SA) augmented tumor-specific targeting and retention of anti-PD-L1, while fucoidan reprogrammed the immune microenvironment, thereby synergizing with the anti-PD-L1 to increase CD8 + T cell infiltration and enhance radio-immunotherapy efficacy. This work exemplifies a novel paradigm for brain-targeted precise drug delivery.
研究领域:
纳米医学
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肿瘤学
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免疫治疗
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放射治疗
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药物递送系统
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生物医学工程
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JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Zhijun Miao,Anan Xu,Gang Shen,Siyi Tang,Jie Luo,Jiajian Yang,Zhe Chen,Jinxian Pu,Tao Yang
Immunogenic cell death (ICD) induced by chemotherapeutics holds promise for cancer therapy, but limited drug penetration across the bladder mucosa and an immune-excluded tumor microenvironment (TME) have hindered success in bladder cancer. Here, we develop fluorinated albumin nanocages as transmucosal delivery vesicles that concurrently target cancer-associated fibroblasts (CAFs) and tumor cells to potentiate chemoimmunotherapy. Surface fluorination enables mucosal penetration, while recognition of secreted protein acidic and cysteine-rich (SPARC) protein ensures selective uptake by CAFs and tumor cells. Encapsulated chemotherapeutics enhance ICD through inhibition of the Bcl-2 pathway, promoting tumor cell death. Simultaneous CAF disruption reduces stromal fibrosis, facilitating anti–PD-L1 antibody delivery and T-cell infiltration. This dual-targeting strategy synergizes ICD with immune checkpoint blockade to eradicate bladder tumors by recruiting cytotoxic T cells and suppressing immunosuppressive phenotypes. Ex vivo studies in freshly resected human bladder tumors further validated the translational potential. Our findings highlight fluorinated albumin nanocages as a versatile transmucosal platform to remodel the tumor–stroma axis and amplify chemoimmunotherapy in bladder cancer.
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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药物递送
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癌症生物学
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JOURNAL OF MEDICINAL CHEMISTRY
·
2024
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IF 6.8
Yan Chen,Ming Zhang,Yanqin He,Suying Li,Shuaiqi Feng,Zhifang Liu,Ning Zhang,Meifeng Liu,Qingpeng Wang
Epithelial–mesenchymal transition (EMT) is a critical process for cancer progression, which is crucial in inhibiting the immunity in tumors and further boosting tumor metastasis. The suppression of EMT represents a promising strategy for inhibiting metastatic tumors. Herein, a series of new canadine platinum(IV) conjugates with potent antiproliferative and antimetastatic activities were developed, which activated by suppressing EMT and provoking immune response in tumors besides causing DNA injury. The complexes could covalently conjugate to DNA and induce mitochondria-mediated apoptosis via Bcl-2/Bax/caspase3 signaling. The EMT process was remarkably inhibited by suppressing the Wnt/β-catenin pathway, reversing the inflammatory tumor microenvironment, and inhibiting the HIF-1α pathway, which further resulted in the inhibited angiogenesis in tumors. Moreover, the antitumor immunity was elevated by blocking immune checkpoints PD-L1 and CD47 accompanied by the improvement of CD3+ and CD8+ T lymphocytes and the macrophage polarization from M2- toward M1-type simultaneously in tumors.
研究领域:
癌症生物学
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药理学
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免疫学
·
分子生物学
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PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Ming Zhang,Yan Chen,Shuaiqi Feng,Yanqin He,Zhifang Liu,Ning Zhang,Qingpeng Wang
The inflammatory microenvironment is a central driver of tumor metastasis, intimately associated with the promotion of epithelial–mesenchymal transition (EMT) and immune suppression. Here, transferrin-modified carprofen platinum(IV) nanoparticles Tf-NPs@CPF2–Pt(IV) with promising antiproliferative and antimetastatic properties were developed, which activated by inhibiting inflammation, suppressing EMT, and activating immune responses besides causing DNA injury. The nanoparticles released the active ingredient CPF2–Pt(IV) in a sustained manner and offered enhanced pharmacokinetic properties compared to free CPF2–Pt(IV) in vivo. Additionally, they possessed satisfactory tumor targeting effects via the transferrin motif. Serious DNA damage was induced with the upregulation of γ-H2AX and P53, and the mitochondria-mediated apoptotic pathway Bcl-2/Bax/caspase3 was initiated. Inflammation was alleviated by inhibiting COX-2 and MMP9 and decreasing inflammatory cytokines TNF-α and IL-6. Subsequently, the EMT was reversed by inhibiting the Wnt/β-catenin pathway. Furthermore, the antitumor immunity was provoked by blocking the immune checkpoint PD-L1 and increasing CD3+ and CD8+ T lymphocytes in tumors.
研究领域:
癌症研究
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纳米技术
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药理学
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免疫学
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分子生物学
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PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Jingyi Liu,Qing You,Siyuan Ye,JinJin Wang,Rong Du,Fuming Liang,Zhaohui He,Chen Wang,Ling Zhu,Yanlian Yang
Photothermal therapy (PTT) can mediate the immunogenic cell death (ICD) of tumors through photothermal transformation, thus releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) to stimulate the maturation of dendritic cells (DCs) and elicit the immune response against tumors. However, PTT-mediated upregulation of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) will cause the immune evasion of tumor cells and thus increases the immunosuppression of cytotoxic T lymphocytes (CTLs), resulting in restricted photothermal immune activation. Taking advantage of the high expression of programmed cell death protein 1 (PD-1) in T lymphocytes, we develop an immunogenic photothermal hybrid nanovesicle to reverse immunosuppression and enhance PTT-induced ICD. The hybrid vesicle (TMVL-I) is constructed by phospholipid bilayer fusion of T cell-derived membrane vesicle (TMV) with high PD-1 expression and the indocyanine green (ICG)-loaded thermosensitive liposome (L-I). TMVL-Is bind to the tumor cells with PTT-induced upregulation of PD-L1, effectively blocking the PD-1/PD-L1 pathway between CTLs and tumor cells, thus reversing PD-L1-mediated tumor immunosuppression and intensifying photothermal-induced ICD effects. These processes significantly induce the maturation of DCs and enhance the infiltration of CTLs into both primary and distal tumors and the activation of spleen CTLs, strongly inhibiting the growth of B16 xenograft tumors and greatly improving the survival rate of B16 xenograft mice. This work provides a feasible strategy for immunosuppressive microenvironment reprogramming-based combination therapy.
研究领域:
癌症治疗
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纳米技术
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免疫学
·
生物医学工程
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