CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Tianle Zhou,Haoyang Du,Su Zhao,Gen Li,Siyu Wang,Sikai Wang,Jinfeng Ning,Manjie Zhang,Hang Yin
Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality worldwide, with therapeutic progress hindered by the immunosuppressive and heterogeneous tumor microenvironment (TME). Protein arginine methyltransferase 3 (PRMT3), a key regulator of post-translational modifications (PTMs), plays a pivotal role in immune evasion and therapeutic resistance by modulating key oncogenic and immune pathways. Despite the potential of PRMT3 inhibitors, such as SGC707, their clinical efficacy is limited by poor pharmacokinetics, inadequate therapeutic durability, and the complex interplay within the TME. To address these challenges, we developed a multifunctional nanoplatform, poly (acrylic acid)‑copper bismuth tellurium@SGC707 nanospheres (PAA-CuBiTe@SGC707 NSs), which integrates copper-induced cell death (cuproptosis), radiosensitization, and PRMT3 inhibition to achieve synergistic therapeutic outcomes. The nanoplatform induces mitochondrial DNA (mtDNA) release, thereby activating a cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated immunogenic response, which is further amplified by SGC707 through the suppression of PRMT3-mediated arginine methylation of cGAS. Furthermore, the incorporation of Bi and Te nanoparticles endows the nanoplatform with effective radiosensitization capability, improving the precision and efficacy of radiotherapy. This study presents a novel nanotechnology-driven therapeutic strategy that simultaneously addresses immune resistance and radiotherapy limitations, providing a promising approach for improving NSCLC treatment outcomes.
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高影响因子
Cell Reports Medicine
·
2024
·
IF 11.7
Chao Zhang,Yu-Xuan Sun,Ding-Cheng Yi,Ben-Yuan Jiang,Li-Xu Yan,Ze-Dao Liu,Li-Shan Peng,Wen-Jie Zhang,Hao Sun,Zhi-Yong Chen,Dan-Hua Wang,Di Peng,Song-An Chen,Si-Qi Li,Ze Zhang,Xiao-Yue Tan,Jie Yang,Zhang-Yi Zhao,Wan-Ting Zhang,Jian Su,Yang-Si Li,Ri-Qiang Liao,Song Dong,Chong-Rui Xu,Qing Zhou,Xue-Ning Yang,Yi-Long Wu,Ze-Min Zhang,Wen-Zhao Zhong
The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon’s two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro . Infiltration and T cell receptor (TCR) clonal expansion of CCR8 + regulatory T (Treg) hi /CXCL13 + exhausted T (Tex) lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.
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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PubMed
高影响因子
Advanced Materials Interfaces
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2026
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IF 4.5
Chunmin Jia,Yimin Lei,Hong Xu,Xin Meng,Yuxiang Wei,Peixian Li,Xiaohua Ma,Yue Hao,Xiaohui Jia
Programmed death-1 (PD-1) is a key biomarker for monitoring therapeutic response and resistance in non-small cell lung cancer (NSCLC) immunotherapy. Achieving highly sensitive, real-time detection of PD-1 is crucial for early prediction of treatment resistance and disease recurrence. However, current methods such as ELISA suffer from limitations in sensitivity, speed, and cost. To address these challenges, we develop a label-free biosensor based on semiconducting single-walled carbon nanotube field-effect transistors (CNT-FETs). The sensing interface is designed by wrapping s-SWCNTs with poly[9-(1-octylnonyl)-9H-carbazole] (PCz), enabling immobilization of anti-PD-1 antibodies via cation-π interactions. XPS analysis confirms antibody immobilization via reversible binding energy shifts in C 1s and N 1s spectra upon salt treatment, consistent with cation-π interactions, further validated by NaCl and imidazole competition assays. Using this strategy, the sensor achieves a detection limit of 8.39 fg/mL for murine PD-1—three orders of magnitude lower than ELISA, along with good specificity and favorable regeneration capability. In human serum, it shows promising performance, with 12 out of 14 NSCLC patient samples (85.7%) exhibiting good linear correlation. With rapid response, low cost, and simple operation, this platform offers a reliable strategy for point-of-care PD-1 monitoring during NSCLC immunotherapy.
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ANALYTICAL CHEMISTRY
·
2025
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IF 6.7
Kai Wang,Lu Fan,Zhen-Zhen Pan,Yun Guo,Jie-Li Zhou
This study introduces HD-LACTB (Hemicyanine Dye-LACTB), a novel near-infrared fluorescent probe designed for real-time imaging of β-lactamase (LACTB) activity in nonsmall cell lung cancer (NSCLC). HD-LACTB incorporates a semicyanine-based signal-reporting unit that undergoes structural activation upon interaction with LACTB, enabling sensitive fluorescence detection. Compared to previous probes, HD-LACTB exhibits superior deep-tissue penetration, high selectivity, and low cytotoxicity, making it well-suited for in vivo applications. The probe effectively targets the mitochondria and enables intracellular imaging of LACTB activity during tumor induction and drug treatment. In both subcutaneous and orthotopic lung cancer mouse models, HD-LACTB demonstrated consistent and robust performance, accurately visualizing LACTB-mediated metabolic alterations. These results highlight the clinical potential of HD-LACTB as a noninvasive tool for early diagnosis, tumor staging, therapeutic monitoring, and personalized treatment assessment in NSCLC.
研究领域:
癌症研究
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生物成像
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分子诊断
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荧光探针
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诊疗一体化
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DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 7
·1077
·
IF 4.8
Xinyi Lv,Yuehan Song,Tianhua Liu,Dingdan Zhang,Xinpeng Ye,Qingqing Wang,Rongrong Li,Jiayi Chen,Shujing Zhang,Xue Yu,Chunying Hou
Background : Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, there is an urgent need to find strategies to increase their efficacy and reduce the incidence of drug resistance. Methods : In this study, we examined the distribution and probability of EGFR mutations in non-small cell lung cancer patients in the cBioPortal database and compared the survival prognosis of patients with normal and abnormal EGFR, NSCLC patients treated with and without TKI, and NSCLC patients with different EGFR gene copy numbers. We established a mouse lung cancer model and examined the histomorphological characteristics of lung tissues via hematoxylin and eosin staining. Additionally, changes in the copy number of the EGFR gene and its protein expression levels were detected using RT-qPCR and Western blotting. Furthermore, we quantified the concentration of the EGFR protein using ELISA. Results : We found no significant advantage of EGFR-TKI therapy over first-line chemotherapeutic agents in patients with EGFR-abnormal NSCLC. The reason for this may be related to the abnormal EGFR gene copy number; the higher the copy number increases, the worse the survival prognosis of the patients. In molecular biology experiments, we demonstrated that ginsenoside Rg3 down-regulated the copy number of 18, 19, 20, and 21 exons and protein expression of EGFR in lung adenocarcinoma cells. The results of in vivo pharmacodynamic assays confirmed that sequential administration of ginsenoside Rg3 with TKI drugs could achieve a gainful complementary effect. Conclusions : Ginsenoside Rg3 down-regulates the copy number of EGFR important exons in EGFR-mutant cells of lung adenocarcinoma and reduces EGFR protein expression, thus providing a high gainful complementary effect in combination with EGFR-TKI.
研究领域:
肿瘤学
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药理学
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分子生物学
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遗传学
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药物研发
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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
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IF 5.6
Yuan-yuan Zhai,Qiang Wang,Qi-yao Nong,Mei-yu Gao,Ying Zhang,Qin-wen Xiao,Yuan Tian,Zun-jian Zhang,Feng-guo Xu,Pei Zhang
Multidrug resistance (MDR) is a significant challenge in cancer treatment, with limited effective strategies available. Neuropilin-1 (NRP1) is emerging as a potential therapeutic target for overcoming drug resistance, but its role in MDR and the identification of potential inhibitors require further exploration. In this study, we investigated the role of NRP1 in MDR and identifies potential inhibitors targeting NRP1. Elevated NRP1 expression was observed in oxaliplatin (OXP)-resistant HCT116 (HCT116/L) and cisplatin (DDP)-resistant A549 cells (A549/DDP). Virtual screening and biological assays identified pitavastatin (Ptv) as a potent NRP1 inhibitor that restored chemosensitivity in resistant cells both in vitro and in vivo . Mechanistic studies revealed that Ptv directly binds to NRP1, promotes degradation of Zinc finger X-chromosomal protein (ZFX), and disrupts the NRP1-ZFX axis to reverse MDR. This study provides promising prospects for targeting the NRP1-ZFX axis as a therapeutic strategy for MDR and highlights the potential clinical application of Ptv in diseases involving NRP1.
研究领域:
癌症生物学
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药理学
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分子生物学
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肿瘤学
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药物研发
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DOI
PubMed
高影响因子
APOPTOSIS
·
2026
·Vol. 31
·期 3
·78
·
IF 9
Huang Xiaofeng,Shen Fei,Wang Dengshu,Wen Yaojuan,Zhang Yunqiang,Sheng Ning,Jiang Xuewei,Wu Song,Mi Yedong
Non-small cell lung cancer (NSCLC) metastasis, driven by tumor-associated macrophages (TAMs), remains a significant challenge due to poor prognosis and limited therapeutic options. This study developed DSPE-PEG-M2pep-modified liposomal nanoparticles (M2pep-LNP@siITGB4) delivering siRNA targeting integrin β4 (siITGB4) to reprogram M2 TAMs and induce apoptosis in NSCLC cells, thereby inhibiting metastasis. Cationic liposomes were prepared using thin-film hydration and ultrasonic emulsification, with M2pep peptides enhancing targeted delivery to M2 macrophages. In vitro, THP-1-derived M2 macrophages were co-cultured with A549 and NCI-H1299 cells, and the effects on macrophage polarization and tumor cell behavior were assessed via RT-qPCR, Western blot, and Transwell assays. In vivo, A549 xenograft and lung metastasis models were analyzed using IVIS, flow cytometry, and RNA sequencing. M2pep-LNP@siITGB4 downregulated M2 markers (CD206, Arg1, IL-10), upregulated M1 markers (CD86, iNOS), and increased CD8 + T cell infiltration. Silencing ITGB4 reduced GNB5 expression and FAK/Src/AKT phosphorylation, promoting apoptosis and inhibiting epithelial-mesenchymal transition (EMT). RNA-seq revealed 3494 differentially expressed genes, with suppressed ECM-receptor interactions. Tumor volumes and metastatic lesions were significantly reduced. This approach effectively reprograms TAMs, induces tumor cell apoptosis, and suppresses NSCLC metastasis, offering a novel nanomedicine-based strategy for enhancing anti-tumor immunity and improving therapeutic outcomes in NSCLC. Graphical abstract Schematic illustration of the mechanism by which M2pep-LNP@siITGB4 silences ITGB4 to modulate the integrin-FAK/Src-AKT signaling axis, reprogram macrophage polarization, and inhibit EMT (created with BioRender).
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-13
·
IF 10.435
Yin Yipengchen,Li Yongjing,Wang Sheng,Dong Ziliang,Liang Chao,Sun Jiaxin,Wang Changchun,Chai Rong,Fei Weiwei,Zhang Jianping,Qi Ming,Feng Liangzhu,Zhang Qin
Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T 1 -weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.
研究领域:
纳米技术
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生物医学工程
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肿瘤学
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-19
·
IF 7.5
Hu Songliu,Zhan Ning,Li Jian,Wang Liqun,Liu Yiyan,Jin Ke,Wang Yixuan,Zhang Juxuan,Chen Yiyang,Bai Yang,Wang Yichong,Qi Lishuang,Liu Shilong
Background Radiotherapy is commonly used for locoregionally advanced NSCLC, but radioresistance is a clinical challenge. The long non-coding RNA CBR3-AS1 mediates radioresistance in NSCLC, yet the underlying molecular mechanism is unclear. This study aims to explore whether and how N6-methyladenosine (m6A) modification regulates CBR3-AS1 expression and promotes NSCLC radioresistance. Methods Integrative bioinformatics analyses were used to investigate the m6A methyltransferases that were associated with CBR3-AS1 expression and radioresistance of patients using data from The Cancer Genome Atlas of lung adenocarcinoma and squamous cell carcinoma. Clinical samples of 133 patients with NSCLC was collected to validate the correlation of the methyltransferase with radioresistance. The functional role and molecular mechanism of the methyltransferase in radioresistance was investigated through a series of in vitro experiments including m6A MeRIP-PCR, lentivirus transfection, RNA immunoprecipitation, Luciferase reporter, Colony formation, Transwell invasion, Flow cytometry, ELISA and TUNEL assay and in vivo experiments. Results The methyltransferase RNA binding motif protein 15 (RBM15) was identified as it was significantly positively correlated with CBR3-AS1 expression and overall survival of NSCLC patients receiving radiotherapy. The clinical samples demonstrated that the high protein expression of RBM15 was significantly enriched in patients with radioresistance as well as associated with poor prognosis of patients receiving radiotherapy. In vitro, RBM15 silencing enhanced the effects of radiation on the growth and invasion inhibition, and apoptosis induction of NSCLC cells; RBM15 overexpression had the opposite effects. Mechanistically, RBM15 induced CBR3-AS1 upregulation via an m6A-IGF2BP3-dependent mechanism, inducing CXCL1 expression by sponging miR-409-3p to recruit myeloid-derived suppressor cells (MDSCs) and inhibit T cell activity. In vivo, RBM15 silencing suppressed MDSC invasiveness and enhanced CD8 + and CD4 + T cell infiltration, causing NSCLC cells to overcome radioresistance. Conclusion Our study identifies methyltransferase RBM15 as a potential therapeutic target for NSCLC radioresistance whose inhibition reverses resistance through limiting MDSC recruitment via the m6A-IGF2BP3-CBR3-AS1/miR-409-3p/CXCL1 axis. Graphical
研究领域:
肿瘤学
·
分子生物学
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表观遗传学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 4.7
Zhen-Peng Yu,Ke-Xin Sun,Dan Zhang,Zhi-Qiang Yu,Deng-Yun Chen,Hong Zhu,Hongwei Si,Peng-Fei Dai
Anaplastic lymphoma kinase (ALK) is prominently expressed in numerous malignant tumors, which lead to aberrant tumor proliferation, invasion and metastasis. Ceritinib (LDK378), as second-generation targeted drugs, has been used to treat advanced ALK-positive non-small cell lung cancer (NSCLC). Herein, we sought to develop a novel ALK-positron emission tomography/magnetic resonance (PET/MR) tracer 68 Ga-DOTA-CTB ( 68 Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The 68 Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that 68 Ga-DOTA-CTB could be accumulated in H2228 cells. Imaging and biodistribution experiments have revealed significant uptake of the radiotracer in the tumors of the experimental group, while tumors in the blocking group, which were saturated with an excess of precursor, exhibited a markedly reduced level of radioactivity. These empirical findings suggest that 68 Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.
研究领域:
肿瘤学
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核医学
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分子影像学
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Sirui Liu,Xinlan Bian,Furong Zhao,Min Cao,Zhaoyang Shang,Bingzhi Li,Xing Zhang
High mannose is overexpressed on the cell surface during carcinogenesis; however, there are currently no efficient techniques for its detection. Herein, we propose an assay called RADAR ( r emote high m a nnose d etection on cell surf a ce with C R ISPR) for the quantification of high mannose, leveraging the integration of high mannose-binding aptamer and CRISPR technique. The high mannose-binding aptamer is hybridized with a locker, which is released upon specific binding to high mannose. The released locker then activates CRISPR/Cas12a to produce a fluorescence signal. The "remote" concept in RADAR refers to the recognition of high mannose occurring on the cell surface, while signal generation takes place in a solution separate from the target. This feature makes RADAR suitable for the detection of suspended bio-samples without the need for sophisticated imaging. RADAR can detect high mannose Man 9 with a limit of detection of 2.5 nM, distinguish cancer cells from non-cancerous cells, and profile high mannose level in human serum for potential non-small cell lung cancer (NSCLC) diagnosis. This work represents the first attempt to integrate CRISPR technology into the aptasensing of high mannose, which may serve as a synthetic biology-enabled tool in glycochemistry and glycobiology.
研究领域:
合成生物学
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糖化学
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糖生物学
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生物技术
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癌症诊断
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-11
·
IF 10.6
Liu Jie,Liu Chengxiang,Tang Jinghua,Chen Qiao,Yu Yan,Dong Yan,Hao Jie,Wu Wei
Radiotherapy (RT) is one of the important treatment modalities for non-small cell lung cancer (NSCLC). However, the maximum radiation dose that NSCLC patient can receive varies little. Therefore, the exploitation of novel RT sensitization approaches is a critical need for the clinical treatment. RT resistance in NSCLC is linked to tumor microenvironment (TME) hypoxia, cell cycle arrest and associated genetic alterations. Here, we designed a novel method for targeted delivery of quercetin (QT) and CeO2 to enhance RT sensitivity. We loaded QT into CeO2@ZIF-8-HA nanoparticles to prevent its degradation in the circulatory system and successfully delivered QT and CeO2 targeted to NSCLC tumors. Under the protection and targeted delivery of Zeolitic Imidazolate Framework-8 (ZIF-8), the nanocomplexes exhibited excellent catalytic mimetic activity in decomposing H2O2 into O2, thus significantly reversing the hypoxia of TME, while the radiosensitizer QT caused DNA damage directly after RT. In a subcutaneous tumor model, CeO2@ZIF-8-HA overcame radiation resistance and enhanced therapeutic efficacy. This multiple sensitization strategy combining delivery of QT and CeO2@ZIF-8-HA nanozymes opens a promising approach for RT of NSCLC.
研究领域:
肿瘤学
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纳米技术
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放射肿瘤学
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分子生物学
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PubMed
高影响因子
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