EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Xian Tang,Jingdong Rao,Sheng Yin,Jiaojie Wei,Chunyu Xia,Man Li,Ling Mei,Zhirong Zhang,Qin He
The Cancer-Immunity Cycle is a series of anticancer immune responses initiated and allowed to proceed and expand iteratively. Paclitaxel (PTX) is a classic chemotherapeutic agent, which could induce immunogenic cell death (ICD) to trigger the Cancer-Immunity Cycle. However, the Cycle is severely impaired by tumor cell immunosuppression of host T cell antitumor activity through the programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) (PD-1/PD-L1) immune checkpoint pathway. Here, we demonstrated that PTX mediated the Cancer-Immunity Cycle could be enhanced by PD-L1 knockdown (KD) and followed mTOR pathway inhibition in tumor cells. PD-L1 siRNA (siP) and the hydrophobic chemotherapy drug PTX were co-delivered with a rationally designed hybrid micelle (HM). We showed clear evidence that the HM-siP/PTX is capable of delivering siP and PTX simultaneously to the B16F10 cells both in vitro and in vivo . We demonstrated that HM-PTX/siP reduced the expression of PD-L1 and p-S6K (a marker of mTOR pathway activation) both in vitro and in melanoma-bearing mice and attenuated synergistically tumor growth by chemical toxicity , promoting cytotoxic T-cell immunity and suppressing the mTOR pathway.
研究领域:
肿瘤学
·
免疫治疗
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Yuping Liu,Beibei Zhang,Xueyuan Wu,Fan Wang,Zhiyi Yang,Mengyi Li,Kaixuan Sheng,Yue Yan,Liang Zhu,Hui Jing,Yanmin Wu,Lili Hu,Yanyan Yu,Chenglin Li
Programmed cell death 1 ligand 1 (PD-L1) immunotherapy holds a pivotal role in lung cancer treatment. However, current methods for monitoring PD-L1 expression exhibit several limitations, including hysteresis and the invasive nature of tissue sampling. Circulating tumor cells (CTCs), the important biomarkers in liquid biopsy, are minimally invasive and facilitate continuous monitoring. Consequently, integrating CTC counting with PD-L1 expression analysis offers more comprehensive insights for the development of personalized treatment strategies development and efficacy evaluations. In this study, we presented a facile liquid biopsy assay designed for the dynamic monitoring of PD-L1 expression on CTCs captured from non-small cell lung cancer (NSCLC) patients. This assay was achieved by fabricating two high-performance probes: EpCAM and Vimentin dual-aptamer modified nitrogen-doped carbon quantum dots probe (E/V-apt-N-CQDs) and hairpin PD-L1 aptamer coupled with gold nanoparticles (PD-L1-apt-AuNPs). The E/V-apt-N-CQDs probe effectively captured two types of CTC models (H1299 and A549) exhibiting differential PD-L1 expression. Additionally, reagent-less detection of PD-L1 levels on CTCs was achieved using a portable magnetic electrochemical sensor with excellent specificity and sensitivity, which was capable of measuring PD-L1 concentrations as low as 2 ng/mL. Finally, this assay was applied in 41 NSCLC patients to investigate the correlation between CTC numbers or PD-L1 expression and disease progression and immunotherapy efficacy. The results indicated a significant association between elevated CTC counts or reduced PD-L1 levels and clinical progression. Moreover, this liquid assay successfully monitored dynamic changes in CTCs and PD-L1 expression in NSCLC patients receiving immunotherapy, indicating its potential for clinical application.
研究领域:
医学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Mingli Ye,Qi Niu,Lu Yan,Jianzhou Feng,Lingling Wu,Xiaoya Hu,Qin Xu,Yun Shu
Programmed death ligand 1 (PD-L1) of tumor-derived extracellular vesicles (T-EVs) is an important biomarker to predict immunotherapy response. The traditional bioassays of T-EVs PD-L1 are limited by the detection specificity because of the distribution of the signals by PD-L1 from nontumor-derived EVs, which leads to unsatisfactory predictive accuracy. In this work, we developed a simple and ultrasensitive method for the quantification of T-EVs PD-L1 by using the lipid bilayer magnetic interface as the isolation and enrichment carrier along with hybridization chain reaction (HCR) for signal amplification in a paper-based device. First, magnetic beads were covered by liposome bilayers and then anchored with the cholesterol modified epithelial cell adhesion molecule (EpCAM) aptamer to construct a fluid multivalent magnetic interface and realize the high-performance isolation of T-EVs. Moreover, the biosensor relied on the PD-L1 aptamer to initiate the HCR of EVs. Benefiting from the high isolation ability of the lipid bilayer magnetic interface and the high signal amplification ability of HCR, the dual-aptamer-based biosensor is capable of highly sensitive detection of T-EVs with a detection limit as low as 5.0 EVs·µL −1 in a paper-based device. Overall, the paper-based lipid bilayer magnetic interface biosensor not only can serve as an alternative tool for predicting the immunotherapy response but also displays great potential in point-of-care disease diagnosis.
研究领域:
生物医学工程
·
分子生物学
·
癌症研究
·
即时诊断
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 20
·2200938
·
IF 11.092
Lei Zhou,Haifeng Liang,Yuxiang Ge,Wang Ding,Qing Chen,Taiwei Zhang,Lan Xiao,Yulin Li,Jian Dong,Xiaowen He,Fengfeng Xue,Libo Jiang
Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin β 3 ( β 3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles (ZnPP@MSN-RGDyK) are fabricated. The ZnPP@MSN-RGDyK nanoparticles precisely target β 3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that ZnPP@MSN-RGDyK is a promising immunotherapeutic agent for treating NSCLC-SM.
研究领域:
肿瘤学
·
纳米技术
·
免疫学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yali Wu,Wenjuan Chen,Jingjing Deng,Xingyu Zhou,Jiangbin Chen,Zimo Yang,Xinghui Cao,Jiatong Liu,Qi Tan,E. Zhou,Minglei Li,Mengfei Guo,Yang Jin
Cancer immunotherapy has transformed cancer treatment, demonstrating the potential for lasting responses in multiple solid and hematologic malignancies and thus has revolutionized cancer treatment in clinic. However, the intricate tumor microenvironment (TME), characterized by a rigid extracellular matrix (ECM) and robust immunosuppressive environment, presents substantial hurdles to the effectiveness of cancer immunotherapy. Thus, cancer-associated fibroblasts (CAFs), the most abundant stromal cells that mediate ECM remodeling and participate in immune suppression, represent promising therapeutic targets for combination immunotherapy. In this study, by using and analyzing single-cell RNA-sequencing (scRNA-seq) in the public datasets, we have identified the elevated expression of glucose transporter 1 (GLUT1) in activated CAF subgroups within tumor sites compared to normal tissues. Moreover, the recent literature has also demonstrated that CAFs undergoing high metabolic levels have been identified to show a better response to immunotherapy. Furthermore, extracellular vesicles (EVs) secreted by CAFs remain unexplored, and their role in drug transport systems and targeting efficiency towards tumorous cells remains uninvestigated. Herein, we identified the elevated expression of glucose transporter 1 (GLUT1) as a prognostic indicator for cancer associated with poor prognosis and investigated the vulnerability of lung tumor cell lines and CAFs to pharmacological GLUT1 inhibition with BAY-876. Based on the possibility of targeting the intrinsic TME-associated metabolism by GLUT1 inhibition, we have firstly employed CAFs-derived extracellular vesicles (cEVs) as a carrier for targeted delivery of BAY-876 into GLUT1-high CAFs and tumor cells. The cEV-BAY-876 (cEV B6) treatment significantly resulted in glucose-rich, low-lactate TME, reversed the activated CAFs phenotype, enabled stromal reprogramming, decreased ECM stiffness and enhanced the infiltration of CD3 + CD8+ T cells in tumor core, thereby achieving an excellent anti-tumor efficiency. Moreover, cEV-B6 treatment synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes and exerted strong anticancer effects against mice lung tumors. Our study provides the first evidence that tumor stroma-specific therapies by targeting glucose metabolism present a promising strategy of remodeling the extracellular matrix to reverse CAFs into normal type and potentiate cytotoxic T lymphocytes (CTLs) infiltration thereby improving anticancer immunotherapy.
研究领域:
肿瘤生物学
·
免疫治疗
·
代谢调控
·
生物材料与递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-13
·
IF 16.6
Wang Shenqiang,Zhang Ying,Wang Yanfang,Yang Yinxian,Zhao Sheng,Sheng Tao,Zhang Yuqi,Gu Zhen,Wang Jinqiang,Yu Jicheng
Immune checkpoints play key roles in maintaining self-tolerance. Targeted potentiation of the checkpoint molecule PD-L1 through in situ manipulation offers clinical promise for patients with autoimmune diseases. However, the therapeutic effects of these approaches are often compromised by limited specificity and inadequate expression. Here, we report a two-step dual-anchor coupling strategy for enhanced immobilization of PD-L1 on target endogenous cells by integrating bioorthogonal chemistry and physical insertion of the cell membrane. In both type 1 diabetes and rheumatoid arthritis mouse models, we demonstrate that this approach leads to elevated and sustained conjugation of PD-L1 on target cells, resulting in significant suppression of autoreactive immune cell activation, recruitment of regulatory T cells, and systematic reshaping of the immune environment. Furthermore, it restores glucose homeostasis in type 1 diabetic mice for over 100 days. This specific in situ bioengineering approach potentiates the functions of PD-L1 and represents its translational potential.
研究领域:
免疫学
·
生物医学工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 19
·8998-9008
·
IF 7.79
Xupeng Mu,Meng Zhang,Anhui Wei,Fei Yin,Yan Wang,Kebang Hu,Jinlan Jiang
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA–DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA–DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA–DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
研究领域:
癌症研究
·
纳米技术
·
药学
·
免疫治疗
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Saijun Wang,Zaigang Zhou,Rui Hu,Mingyue Dong,Xiaobo Zhou,Siyan Ren,Yi Zhang,Chengxun Chen,Ruoyuan Huang,Man Zhu,Wanying Xie,Ling Han,Jianliang Shen,Congying Xie
At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand-1 (PD-L1) expression. Incredibly, intracellular PD-L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD-L1function still limits the effectiveness of radio-immunotherapy. Therefore, better PD-L1 regulation strategies are still urgently needed to better sensitize radio-immunotherapy. Hence, for this purpose, TPP-LND is synthesized by linking mitochondrial-targeted triphenylphosphine cations (TPP + ) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µ M ). Then, TPP-LND is wrapped with liposomes to form TPP-LND@Lip nanoparticles. By doing this, TPP-LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD-L1 via enhancing the adenosine 5′-monophosphate-activated protein kinase activation. As expected, these well-designed economical TPP-LND@Lip nanoparticles are more effective than conventional anti-PD-L1 antibodies to some extent.
研究领域:
肿瘤学
·
药理学
·
放射生物学
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Tongfang Chen,Jingjie Liang,Weiqing Liu,Xiaorong Luo,Fengxia Zhou,Yingchun Zhou,Shan Xing
Background Colorectal cancer (CRC) requires accurate diagnostic approaches for effective clinical management. Serum biomarkers PD-L1, SORL1, and GDF-15 offer valuable diagnostic information, but their simultaneous detection is hindered by the limited sensitivity and multiplexing capacity of conventional immunoassays. This work addresses the critical need for a highly sensitive multiplexed platform for precise CRC diagnosis. Results We constructed a multicolor QDs-K@FLISA platform employing K24 polylysine-conjugated CdTe quantum dots with distinct emissions (543/587/647 nm). The K-peptide enabled multi-QD loading, significantly amplifying fluorescence signals and facilitating ultrasensitive triplex detection. The assay achieved exceptional sensitivity with detection limits of 0.996 pg/mL (PD-L1), 1.101 pg/mL (SORL1), and 1.035 pg/mL (GDF-15), along with wide linear ranges (7.8-500 pg/mL for PD-L1/SORL1; 6-1600 pg/mL for GDF-15). High reproducibility was demonstrated (RSD < 2.3%). Clinical validation using 120 serum samples revealed strong correlation with reference methods (R 2 > 0.99) and effective discrimination between CRC patients and healthy controls. Significance and Novelty This work establishes a novel peptide-mediated multi-QD loading strategy that enables ultrasensitive multiplexed detection of CRC biomarkers. The platform presents significant potential for clinical applications in CRC diagnosis and biomarker profiling.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Guan Xin,Sun Liping,Shen Yuting,Jin Fengshan,Bo Xiaowan,Zhu Chunyan,Han Xiaoxia,Li Xiaolong,Chen Yu,Xu Huixiong,Yue Wenwen
Cancer recurrence after surgical resection (SR) is a considerable challenge, and the biological effect of SR on the tumor microenvironment (TME) that is pivotal in determining postsurgical treatment efficacy remains poorly understood. Here, with an experimental model, we demonstrate that the genomic landscape shaped by SR creates an immunosuppressive milieu characterized by hypoxia and high-influx of myeloid cells, fostering cancer progression and hindering PD-L1 blockade therapy. To address this issue, we engineer a radio-immunostimulant nanomedicine (IPI549@HMP) capable of targeting myeloid cells, and catalyzing endogenous H 2 O 2 into O 2 to achieve hypoxia-relieved radiotherapy (RT). The enhanced RT-mediated immunogenic effect results in postsurgical TME reprogramming and increased susceptibility to anti-PD-L1 therapy, which can suppress/eradicate locally residual and distant tumors, and elicits strong immune memory effects to resist tumor rechallenge. Our radioimmunotherapy points to a simple and effective therapeutic intervention against postsurgical cancer recurrence and metastasis.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
放射肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Exploration
·
2025
·
IF 22.5
Qi Lu,Hao Ye,Jian Zhao,Xiaoyuan Fan,Kaiyuan Wang,Zeyu Han,Tian Liu,Lili Du,Jiaxuan Song,Helin Wang,Haotian Zhang,Zhonggui He,Jin Sun
The tumor microenvironment is characterized by immunosuppression and compromised intratumoral perfusion, which impairs the effectiveness of immune checkpoint inhibitors and nanomedicines. A significant challenge is the role of activated platelets, as they increase transfer-mediated PD-L1 expression from tumor cells and maintain the integrity of tumor vasculature. These platelets support tumor growth by stabilizing the vasculature and enabling immune evasion, as well as shielding tumor cells from immune detection. To address these platelet-mediated negative antitumor effects, we have developed bioengineered platelets (PTNPs) with surface-anchored ticagrelor-loaded gelatin nanoparticles. This study utilizes the natural tendency of platelets to localize their activated counterparts into tumors. Upon binding to tumor-associated activated platelets, the PTNPs release ticagrelor in response to the secreted matrix metalloproteinases by activated platelet, inhibiting further platelet activation. This reduction in platelet activation lessens platelet-facilitated immunosuppression and diminishes the transferred-PD-L1 expression from cancer cells to platelets, thus enhancing the immune response of anti-PD-L1 therapy. Additionally, this strategy weakens the activated platelets’ contribution to tumor vascular integrity, improving the extravasation and chemotherapeutic efficacy of nanomedicines. Our findings highlight the crucial role of platelet activation in tumor biology and introduce PTNPs as an effective approach to disrupt tumor-supporting platelet activities and enhance anticancer treatments efficacy.
研究领域:
肿瘤生物学
·
免疫治疗
·
纳米医学
·
药理学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yan Gao,Zilin Song,Li Jia,Yi Tang,Chengcheng Wang,Xiuli Zhao,Haiyang Hu,Dawei Chen,Mingxi Qiao
Despite the important role of reactive oxygen species (ROS) in battling cancer, ROS production with current approaches has been severely limited by the deficiency of oxy-substrates in tumor microenvironment . Herein, an atorvastatin (Ato)-catalytic self-amplified approach was utilized for sustainable ROS production and enhancing anti-tumor efficacy of PD-L1 silencing. A C 18 -pArg 8 -ss-pHis 10 lipopeptide based self-assembled nanoplexes was developed to co-encapsulate AMP-activated protein kinase (AMPK) activator of Ato and PD-L1 siRNA. Efficient delivery of payloads was achieved because of the acidic pH triggered the protonation of pHis 10 , disulfide-bond exposure for cleavage and subsequent cytosolic translocation. Ato was found to activate AMPK, boosting the highly restrained mitochondrial fatty acid oxidation (FAO) in cancer cells for ROS production. The ROS derived from FAO further activated AMPK, creating a positive-feedback mechanism of sustainable ROS production. The self-amplified ROS production from cellular mitochondrial FAO was maintained by the sufficient intracellular fatty acid substrates arising from the dysregulated lipid metabolism and Ato inhibited triglyceride synthesis in cancer cells. The excessive ROS level was found to successfully induce immunogenic cell death effect, boosting the anti-tumor efficacy of PD-L1 silencing. Overall, the Ato catalyzed self-amplified ROS production has been demonstrated as a promising alternative for cancer therapy.
研究领域:
癌症治疗
·
药学
·
免疫学
·
分子生物学
✓ 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）