BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Qianqian Wang,Xin Yuan,Cuijuan Liu,Ying Huang,Lin Li,Yimin Zhu
CAR-T cell therapy has been proven to be effective on hematological tumors, although graft-versus-host disease and cytokine release syndrome(CRS) limit its application to a certain extent. However, CAR-T therapy for solid tumors met challenges, among which the lack of tumor-specific antigens (TSA) and immunosuppressive tumor microenvironment (TME) are the most important factors. CAR-NK could be a good alternative to CAR-T in some ways since they can induce mild CRS and are independent of HLA-matching, but the efficacy of CAR-NKs remains limited in solid tumors. CAR cells armed with multiple tumor targeting molecules may obtain higher therapeutic efficacy against solid tumors. Due to large molecular weight, multivalent scFvs cannot be displayed efficiently on T cells and the high affinity of scFv to the target makes it easy to cause on-target, off-tumor(OTOT) toxicity. Peptides with low molecular weight and slightly lower affinity than scFvs allow immune cells to display multiple peptides to increase killing ability and reduce OTOT toxicity. In our study, peptide-based CAR-NK cells were designed to solve the dilemma of CAR-T in solid tumors. Firstly, the peptide-based CAR-NK92MI cells with A1 peptide were constructed and their inhibitory effects on the growth of A549 tumor cells were identified. Secondly, the tri-specific CAR-NK92MI cells with peptides that simultaneously targeted PD-L1, EGFR and VEGFR2 were developed for the combinatory therapy. Tri-specific CAR-NK92MI exhibited comparable killing activities to scFv-based CAR-NK92MI. Moreover, peptide-based CAR NK92MI mitigated OTOT toxicity. Our study implied that peptide-based CAR-NKs could behave as promising tools in solid tumor
研究领域:
免疫学
·
肿瘤学
·
细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2015
·Vol. 10
·期 3
·e0121293
·
IF 3.234
Yun Zeng,Yang Liu,Jin Shang,Jingwen Ma,Rong Wang,Lei Deng,Youmin Guo,Fan Zhong,Mingfeng Bai,Shaojuan Zhang,Daocheng Wu
Objectives
To utilize phosphorescence to monitor hypoxic microenvironment in solid-tumors and investigate cancer chemotherapeutic effects in vivo .
Methods
A hypoxia-sensitive probe named BTP was used to monitor hypoxic microenvironment in solid-tumors. The low-dose metronomic treatment with cisplatin was used in anti-angiogenetic chemotherapeutic programs. The phosphorescence properties of BTP were detected by a spectrofluorometer. BTP cytotoxicity utilized cell necrosis and apoptosis, which were evaluated by trypan blue dye exclusion and Hoechst33342 plus propidium iodide assays. Tumor-bearing mouse models of colon adenocarcinoma were used for tumor imaging in vivo . Monitoring of the hypoxic microenvironment in tumors was performed with a Maestro 2 fluorescence imaging system. Tumor tissues in each group were harvested regularly and treated with pathological hematoxylin and eosin and immunohistochemical staining to confirm imaging results.
Results
BTP did not feature obvious cytotoxicity for cells, and tumor growth in low-dose metronomic cisplatin treated mice was significantly inhibited by chemotherapy. Hypoxic levels significantly increased due to cisplatin, as proven by the expression level of related proteins. Phosphorescence intensity in the tumors of mice in the cisplatin group was stronger and showed higher contrast than that in tumors of saline treated mice.
We develop a useful phosphorescence method to evaluate the chemotherapeutic effects of cisplatin. The proposed method shows potential as a phosphorescence imaging approach for evaluating chemotherapeutic effects in vivo , especially anti-angiogenesis.
研究领域:
肿瘤学
·
医学影像学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 45
·19109-19122
·
IF 7.79
Songbo Zhao,Jiazhi Duan,Yalin Lou,Ruyun Gao,Shanshan Yang,Piming Wang,Chunhua Wang,Lin Han,Minghuan Li,Chunhong Ma,Xiaohong Liang,Hong Liu,Yuanhua Sang,Lifen Gao
Although there has been significant progress in the development of tumor immunotherapies, many challenges still exist for the treatment of solid tumors. Natural killer (NK) cells possess broad-spectrum cytotoxicity against tumors, but their limited migration and infiltration abilities restrict their application in solid tumor therapies. Here, we combined a facile and efficient magnetic-targeting strategy with NK cell-based therapy to develop a novel immunotherapy approach for treating solid tumors. Anti-CD56 antibodies were conjugated with Fe3O4 nanoparticles, which could specifically bind with NK-92 cells endowing them with a magnetic field driven targeting ability. These NK–Fe3O4 biohybrid nanoparticles were able to facilitate directional migration to the tumor site in vivo under external magnetic field guidance and efficiently inhibit tumor growth. These functionalized NK cells represent a novel approach for solid tumor therapy and may provide a promising modality for cancer interventions in the future.
研究领域:
生物技术
·
免疫学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Luhan Lin,Hongli Zhao,Jian Hou,Minbo Lan
Hydrogen peroxide (H 2 O 2 ), a crucial redox signaling molecule and neuromodulator, is closely associated with pathological processes, including cancer progression and neurodegenerative disorders. Current methods for in vivo H 2 O 2 detection, such as fluorescence imaging and chemiluminescence, suffer from the limitation of spatial resolution and invasiveness, which makes it difficult to monitor oxidative stress gradients in deep-seated tumors. Therefore, this research developed an implantable triple-electrode biosensor fabricated via screen-printing technology based on carboxylated multi-walled carbon nanotubes (MWCNT) and Prussian blue (PB) nanocomposites. The biosensor presented dual linear detection ranges of 0.8–1126 μM (R 2 =0.9937) and 1286–3766 μM (R 2 =0.9939) with a 0.47 μM detection limit. It demonstrated a >95% specificity compared with other interfering substances and maintained 93.2% signal retention over 30 days. Particularly, in situ implantation in melanoma-bearing mice with one-week-growth-time solid tumors revealed the H 2 O 2 levels 12- to 18-fold higher than in normal tissues, consistent with cancer-associated oxidative stress mechanisms. This platform addresses challenges such as rapid enzymatic degradation and microenvironmental complexity, enabling invasive profiling of H 2 O 2 detection in solid tumors.
研究领域:
生物医学工程
·
肿瘤学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2017
·Vol. 13
·期 12
·1600954
·
IF 8.643
Shixian Lv,Zhaohui Tang,Wantong Song,Dawei Zhang,Mingqiang Li,Huaiyu Liu,Jianjun Cheng,Wu Zhong,Xuesi Chen
Nanomedicine (NM) cannot penetrate deeply into solid tumors, which is partly attributed to the heterogeneous microenvironment and high interstitial fluid pressure of solid tumors. To improve NM efficacy, there has been tremendous effort developing tumor-penetrating NMs by miniaturizing NM sizes or controlling NM surface properties. But progress along the direction of developing tumor penetrating nanoparticle has been slow and improvement of the overall antitumor efficacy has been limited. Herein, a novel strategy of inhibiting solid tumor with high efficiency by dual-functional, nontumor-penetrating NM is demonstrated. The intended NM contains 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular-disrupting agent, and doxorubicin (DOX), a cytotoxic drug. Upon arriving at the target tumor site, sustained release of DMXAA from NMs results in disruption of tumor vessel functions, greatly inhibiting the interior tumor cells by cutting off nutritional supply. Meanwhile, the released DOX kills the residual cells at the tumor exterior regions. The in vivo studies demonstrate that this dual-functional, nontumor penetrating NM exhibits superior anticancer activity, revealing an alternative strategy of effective tumor growth inhibition.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Select
·
2020
·Vol. 1
·期 5
·547-560
·
IF 0
Fei Kong,Dawei Tian,Jin Zhou,Danyang Yue,Yuying Bai,Zhaojiang Yu,Jiayi Duan,Guixue Wang,Jun Pan
An effective chemotherapy through promoting drug transport in solid tumor is our concern here to avoid surgery and its side effects to our bodies. A drug delivery system, TXT-MNT-hydrogel, is constructed using temperature sensitive hydrogel nanoparticles and hydroxypropyl-β-cyclodextrin (HP-β-CD) to co-deliver mannitol (MNT) and taxotere (TXT). TXT-MNT-hydrogel realizes weight inhibition in mice subcutaneous breast tumor for more 94% and 58% than TXT and a clinical used liposomes paclitaxel (Lipusu), and for more 91.4% and 85% than TXT-MNT and TXT-hydrogel as well. The mechanism is disclosed as (1) controlled taxotere and mannitol release from hydrogel nanoparticles and hydroxypropyl-β-cyclodextrin; (2) MNT shrinks the extracellular matrix of tumor tissue, and enhances the transport and bioavailability of drug in vivo for up to 2.7-fold versus no MNT in tumor surface, and from none to 0.5–2.5-fold versus the tumor surface of no MNT in the middle of tumor tissue in 12 hours, which results severer apoptosis in interior tumor cells than all the counterparts. This study certifies in vivo that the simple and published materials of MNT, TXT, HP-β-CD, and hydrogel in combination functionally augment solid tumor therapy, which provides a reference to construct more efficient drug delivery systems.
研究领域:
肿瘤学
·
药剂学
·
生物材料
·
纳米技术
✓ 已验证
DOI
BIOMATERIALS
·
2019
·
IF 10.273
Fuming Chen,Zhongsheng Zang,Ze Chen,Liao Cui,Zhiguang Chang,Aiqing Ma,Ting Yin,Ruijing Liang,Yutong Han,Zhihao Wu,Mingbin Zheng,Chenli Liu,Lintao Cai
Bacteria-driven drug-delivery systems have attracted great attention for their enhanced therapeutic specificity and efficacy in cancer treatment. YB1, a particularly attractive genetically modified safe Salmonella Typhimurium strain, is known to penetrate hypoxic tumor cores with its self-driven properties while remarkably avoiding damage to normal tissues. Herein, nanophotosensitizers (indocyanine green (ICG)-loaded nanoparticles , INPs) were covalently attached to the surface of YB1 with amide bonds to develop a biotic/abiotic cross-linked system (YB1-INPs) for tumor precision therapy. YB1 microswimmer retained its viability after efficiently linking with INPs. This YB1-INPs treatment strategy demonstrated specific hypoxia targeting to solid tumors, perfect photothermal conversion, and efficient fluorescence (FL) imaging properties. Benefited from the combined contribution of tumor tissue destruction and the bacteria-attracting nutrients generation after photothermal treatment, the bioaccumulation of YB1-INPs was significantly improved 14-fold compared to no photothermal intervention. Furthermore, YB1-INPs pervaded throughout the large solid tumor (≥500 mm 3 ). Under near-infrared (NIR) laser irradiation, YB1-INPs exhibited a dependable and highly efficient photothermal killing ability for eradicating the large solid tumor without relapse. This strategy of bacteria-driven hypoxia-targeting delivery has a great value for large solid tumors therapy with low toxicity and high efficiency.
研究领域:
癌症治疗
·
生物医学工程
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2023
·Vol. 19
·期 11
·1882-1890
·
IF 2.9
Hu Jiansheng,Sun Danli,Feng Qinhui,Wei Liang,Liu Wucai
A sandwich electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) using hollow nanospheres composite material loaded with gold nanoparticles as the signal tag and gold triangular nanoplate as the substrate material. Samples obtained from
pediatric solid tumor tissue and their blood samples were used to detect CEA using this nanoparticle. The hollow nanospheres constructed in this study, provided abundant reaction sites and high catalytic activity, while the loading of Au NPs enhances conductivity and biocompatibility. The
immunosensor has good analytical ability in detecting CEA in the mass concentration range of 1 pg/mL to 50 ng/mL, with a low detection limit (LOD) of 0.37 pg/mL. This novel method provides a valuable tool for rapid clinical detection of CEA in the context of pediatric solid tumors.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
✓ 已验证
DOI
高影响因子
Chemical & Biomedical Imaging
·
2023
·
IF 0
Lu-Lu Chen,Zhi-Gang Wang,Hao Zhang,Li-Ming Chen,Liang Zhao,Zhen-Ya Liu,Wei Zhao,Lin-Han Jiang,Ai-Xin Ma,Xiaohui Yang,Shu-Lin Liu,Shiwu Zhang,Dai-Wen Pang
The growth and metastasis of malignant solid tumors depend closely on new blood vessels. Vasculogenic mimicry provides a special pathway of blood supply during the early growth of malignant tumors, and real-time monitoring of its occurrence and development in vivo is important to clinical applications. However, there are few labels with sufficient brightness and stability in vivo to achieve high spatiotemporal resolution imaging of deep tissue for noninvasive optical detection of vasculogenic mimicry in tumor tissues. In this study, we constructed a high-brightness fluorescent label with fluorescence in the near-infrared-II region, which can be used not only for in vivo tumor imaging but also for tissue section imaging. Real-time high-resolution imaging of tumor vessels has been achieved with PbS quantum dots (QDs) surface-coupled with horseradish peroxidase (HRP) (HRP-QDs) by taking advantage of the low background autofluorescence of tissue at the near-infrared-II wavelength for in vivo and tissue section imaging. Qualitative and quantitative analysis of early blood supply patterns of tumor growth enables monitoring neovascularization to accurate noninvasive identification of benign and malignant solid tumors.
研究领域:
生物医学工程
·
肿瘤学
·
分子影像学
✓ 已验证
DOI
BIOMATERIALS
·
2019
·
IF 10.273
Chen Chen,Weiwei Su,Yanyan Liu,Jiawen Zhang,Changjing Zuo,Zhenwei Yao,Wenbo Bu
Oxygen is known as an irreplaceable gas in the lives of most eukaryotic cells, yet researchers underestimate its importance, as in the case in many studies of tumors. The variable oxygen content of malignant solid tumors increases the difficulty of treatment. Thus, it could be reasonably inferred that the tumor oxygen microenvironment , if efficiently and completely regulated, could bring certain changes to existing therapies. Based on this speculation, an acid-responsive, oxygen-scavenging and anaerobic-sensitizing nanoparticle was designed to regulate the oxygen level of solid tumor by creating an artificial anaerobic environment in our study. The Mg 2 Si core, which acted as a deoxygenating agent, was able to consume tumor oxygen and cause cell dormancy, while the incorporated hydrophobic tirapazamin (TPZ) helped to kill the now-dormant tumor cells. This simple and nontoxic nanoparticle achieved controllable factitious anaerobic circumstance in solid tumor for the first time, displaying the considerable potential and promising application of tumor gaseous microenvironment regulation therapy.
研究领域:
肿瘤学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-13
·
IF 9.429
Luo Zhenyu,Luo Lihua,Lu Yichao,Zhu Chunqi,Qin Bing,Jiang Mengshi,Li Xiang,Shi Yingying,Zhang Junlei,Liu Yu,Shan Xinyu,Yin Hang,Guan Guannan,Du Yongzhong,Cheng Ningtao,You Jian
Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yingbo Jia,Jing Hu,Chaojie Zhu,Zijing Li,Xinyu Yang,Ruitian Liu,Linghui Zeng,Lingxiao Zhang
The poor cancer immunotherapy outcome has been closely related to immunosuppressive tumor microenvironment (TME), which usually inactivates the antitumor immune cells and leads to immune tolerance. Metalloimmunotherapy by supplementing nutritional metal ions into TME has emerged as a potential strategy to activate the tumor-resident immune cells. Herein, we engineered a magnesium-contained nano-aluminum adjuvant (NanoAlum) through hydrolyzing a mixture of Mg(OH) 2 and Al(OH) 3 , which has highly similar components to commercial Imject Alum. Peritumoral injection of NanoAlum effectively neutralized the acidic TME while releasing Mg 2+ to activate the tumor-resident T cells . Meanwhile, NanoAlum also blocked the autophagy pathway in tumor cells and subsequently induced cell apoptosis . The in vivo studies showed that merely peritumoral injection of NanoAlum successfully inhibited the growth of solid tumors in mice. On this basis, NanoAlum combined with chemical drug methotrexate or immunomodulatory adjuvant CpG further induced potent antigen-specific antitumor immunity. Overall, our study first provides a rational design for engineering tumor-targeted nanomodulator from clinical adjuvants to achieve effective cancer metalloimmunotherapy against solid tumors.
研究领域:
肿瘤学
·
免疫疗法
·
纳米技术
·
癌症生物学
✓ 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）