Chemosensors
·
2023
·Vol. 11
·期 7
·397
·
IF 4.2
Xuan Zhao,Xiaolong Zeng,Xinyu Wu,Lihong Shi,Sumin Zhu,Wen Sun
Traditional chemotherapeutic drugs have limitations due to their non-targeted ability toward cancer cells. Stimuli-activatable prodrugs are designed to overcome these obstacles. However, the real-time monitoring of stimuli-activatable theranostic prodrugs still poses challenges. Herein, a prodrug (Fe–SS–HCy), consisting of a ferrocene-modified hemicyanine linked via a disulfide bond, is synthesized for anticancer imaging and therapy. Before activation, the toxicity of Fe–SS–HCy is low. The fluorescence of Fe–SS–HCy is quenched by ferrocene due to photoinduced electron transfer. After being taken up by cancer cells, the intracellular GSH activates Fe–SS–HCy, which releases HCy. The fluorescence of HCy is restored and selectively accumulates in the mitochondria, which further produce reactive oxygen species (ROS) to induce cancer cell death. Thus, this “off-on” fluorogenic HCy presents a new strategy for monitoring prodrug activation in real-time and for enhancing therapeutic efficacy with reduced side effects.Keywords:fluorescent dye;cancer imaging;activatable prodrug;photoinduced electron transfer;cancer therapy;hemicyanine
研究领域:
生物医学
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药物化学
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分子影像学
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产品关联
DOI
高影响因子
PHYSICA B-CONDENSED MATTER
·
2021
·
IF 2.436
Yang Yu,Sai Xu,Muhan Jiang,Ruixin Song,Jie Li,Yuefeng Gao,Xizhen Zhang,Xiangping Li,Hongquan Yu,Baojiu Chen
Upconversion core-shell nanoparticles with dual-function of temperature sensing and photothermal conversion are preferable in diagnose and treatment of cancer. Herein, NaYF 4 :Tm 3+ /Yb 3+ @NaYF 4 :Sm 3+ /Yb 3+ upconversion nanoparticles have been synthesized by a high-temperature thermal decomposition method. XRD and TEM are used to characterize the crystal structure and morphology of the samples. Temperature dependent upconversion spectra are measured under excitation of 980 nm within the scope of 303–498 K. The investigation on temperature sensing properties are on the basis of the luminescence intensity ratio of Tm 3+ . The designed core shell nanoparticles and bare core nanoparticles both have good temperature sensing performances, and the sensing properties of both are similar. Furthermore, the photothermal conversion performances are investigated ground on the power dependent temperature measurement, ethanol evaporation experiment and visual infrared thermal images. It is found that the photothermal conversion ability of the core-shell UCNPs is greatly improved by coating of the NaYF 4 : Sm 3+ /Yb 3+ outer shell.
研究领域:
纳米技术
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生物医学工程
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材料科学
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癌症研究
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xinyi Song,Haipeng Rao,Chunchun Huang,Miaoling Huang,Ying Ma,Jingyu Xin,Jiajia Hou,Zhigang Hu,Lingfeng He,Feiyan Pan,Lingdong Yang,Zhigang Guo
Fumarate hydratase (FH) catalyzes the conversion of fumarate to malate in the tricarboxylic acid cycle. Its deficiency leads to fumarate accumulation, which is associated with kidney cancer metastasis, though the exact mechanisms remain unclear. Here, we identify prolyl 4-hydroxylase beta (P4HB) as a novel fumarate target in FH-deficient cancer cells that promotes migration and invasion. FH knockdown in human renal cancer cells significantly enhanced migratory and invasive capacities by 10- and 8-fold, respectively. Mechanistically, fumarate-induced succination stabilizes P4HB, promoting type I collagen production and enhancing tumor metastasis. P4HB knockdown markedly suppresses FH deficiency-induced metastasis in xenograft models. Fluorescence intensity in the FH knockdown group was about 10-fold higher, and tumor-bearing liver weight was approximately 1.5-fold greater than that in the FH and P4HB co-knockdown group. These results underscore the pivotal role of P4HB in metastasis. Additionally, we reveal NDP52 as a specific autophagy receptor that recognizes and binds to P4HB, mediating its degradation through the autophagy-lysosome pathway. However, succination of P4HB disrupts this recognition, interaction, and degradation, stabilizing P4HB. Together, these findings provide new insights into how fumarate-mediated succination affects P4HB protein stability and cancer metastasis, and suggest that P4HB could serve as a potential therapeutic target in FH-deficient cancers.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Matter
·
2023
·
IF 18.9
Zhiqin Cao,Lanfang Ren,Le Niu,Rui Zhao,Nanhui Liu,Qi Zhuang,Feng Pan,Zhuang Liu,Yiyun Cheng,Yang Yang,Qian Chen
Summary Cancer vaccines have attracted tremendous interest in the field of cancer immunotherapy due to their ability to trigger tumor-specific immune responses to destroy cancer cells. Herein, we demonstrate that dendrimers coordinated with manganese ions (GT-Mn 2+ ) could self-assemble with peptides to form a cancer vaccine, which could be internalized by dendritic cells (DCs) via specific macropinocytosis-dependent and lipid-raft-related pathways and then dissociated gradually to release peptides to achieve efficient antigen cross-presentation and stimulate the cGAS-STING pathway. Additionally, GT-Mn 2+ could package multiple neoantigens to form an effective “personalized” cancer vaccine and has exhibited excellent therapeutic effects when used in combination with anti-PD-L1. Thus, our work presents an innovative peptide carrier to construct an effective “personalized” cancer vaccine that shows great promise to achieve effective cancer immunotherapy for different patients in clinic.
研究领域:
癌症免疫疗法
·
纳米医学
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疫苗学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Yuxin Liu,Ge Zhang,Quanwei Guo,Liyi Ma,Qi Jia,Lidong Liu,Jing Zhou
Multifunctional nanomaterials for cancer diagnosis and therapy have recently prompted widespread concern. To avoid nanotoxicity, the development of novel degradable functional materials must be our main focus. In this study, we firstly developed ethylenediaminetetraacetic acid calcium disodium salt (EDTA)- and bovine serum albumin (BSA)-capped Mn 3 O 4 nanoparticles (MONPs-BSA-EDTA) as a novel inorganic nanomaterials for multifunctional imaging-guided photothermal therapy, which can be degraded in a progress-controlled way by artificially introduced ascorbic acid . The degradation products can also be captured and their excretion accelerated. Careful studies suggested that the toxicity of the MONPs-BSA-EDTA and its degradation products is low. The degradation mechanism also suggests a new method of controlled drug release . The development of artificially controlled degradable inorganic nanomaterials also provides a new way to degrade nanomaterials and minimize ion release , which may have potential applications in cancer theranostics without nanotoxicity.
研究领域:
生物医学工程
·
肿瘤学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 8
·1961
·
IF 4.183
Bing Yu,Qingye Meng,Hao Hu,Tao Xu,Youqing Shen,Hailin Cong
Polymeric micelles (PMs) have been applied widely to transport hydrophobic drugs to tumor sites for cancer treatment. However, the low load efficiency of the drug in the PMs significantly reduces the therapeutic efficiency. We report here that disulfide-linked camptothecin (CPT) as a kind of dimeric drug can be effectively embedded in the core of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) PMs for improving drug-loading efficiency, and PEG can be used as a hydrophilic shell. Moreover, the dimeric CPT-loaded PCL–PEG–PCL PMs exhibited excellent solubility in phosphate-buffered saline (PBS) media and significant cytotoxicity to cancer cells.Keywords:dimeric drug;camptothecin;micelles;cancer therapy
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Cheng Jingliang,Fu Jiewen,Tan Qi,Liu Zhiying,Guo Kan,Zhang Lianmei,He Jiayue,Zhou Baixu,Liu Xiaoyan,Li Dabing,Fu Junjiang
ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.
研究领域:
医学
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分子生物学
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肿瘤学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Lu Zheng,Hua Wang,Peng Zuo,Yueling Liu,Huiying Xu,Bang-Ce Ye
Exosomes are lipid bilayer extracellular vesicles secreted by various types of cells and inherit abundant molecular information from parental cells. Tumor-derived exosomes have been widely recognized as noninvasive biomarkers for early cancer diagnosis and surveillance, but the separation of intact exosomes and detection of exosomal proteins remain challenging. Herein, we proposed a microfluidic chip for specific exosome isolation, integrated with sensitive quantification by a novel PTCDI–aptamer signal switch strategy. To enhance the capture efficiency, an alternating drop-shaped micropillar array was designed to assist the capture of tumor-derived exosomes by Tim4-modified magnetic beads (Tim4 beads) on the chip. Following capture, a chelating agent can easily elute intact exosomes which were further used for profiling exosomal surface proteins by the multiplexed fluorescence turn-on approach. Profiting from the efficient on-chip enrichment of the Tim4 beads and superior fluorescence signal transduction strategy, the detection limit of the analysis platform for HepG2 exosomes is as low as 8.69 × 103 particles/mL with a wide linear range spanning 6 orders of magnitude. Meanwhile, the proposed platform could recognize subtle changes in protein levels on the exosomal surface from various cell lines. More importantly, this strategy is successfully applied to analyze exosomes in human serum to distinguish liver cancer patients from healthy individuals. Combined analysis of different types of biomarkers on the exosomal membrane surface can greatly improve the accuracy of cancer type identification and disease monitoring. We hope that this convenient, rapid, and sensitive platform may become a powerful tool in the field of exosome analysis and early cancer screening.
研究领域:
生物医学工程
·
癌症生物学
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分子诊断
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微流控技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Biology
·
2021
·Vol. 6
·期 2
·2101050
·
IF 0
Sirine Yassine,Nada Alaaeddine
Mesenchymal stem cells (MSCs) have displayed a novel therapeutic strategy for a wide range of diseases and conditions. Their secretome and exosome-based paracrine activity are considered as the main processes harboring their diverse therapeutic properties. Several investigations have examined the effects of MSC-derived exosomes on cancer growth, yet, controversial results have always emerged. Although MSC-derived exosomes are able to rigorously enforce the repression of cancer proliferation and progression, it is shown that MSCs exosomal activity displays numerous protumorigenic effects. This discrepancy over the dual effects of MSCs on cancer growth may be mediated by many factors including experimental design, stem cells origins, culture conditions, in addition to cancer-MSCs cross-talks. Despite the controversial effects of MSCs on carcinogenesis, scientists are able to overcome a number of obstacles by modifying MSCs to deliver antioncogenic miRNAs, anticancer drugs, and oncolytic viruses into tumor sites. This review discusses the controversial effects of MSC-derived exosomes on tumorigenesis, investigates the main causes that underlie this discrepancy, summarizes the pattern of engineered-MSCs, and finally highlights how future studies should advance the research in the field of MSCs-based cancer therapies in order to accelerate the transition from preclinical studies to clinical practice.
研究领域:
细胞生物学
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肿瘤学
·
再生医学
✓ 已验证
DOI
PubMed
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-21
·
IF 12.6
Yang Yi,Guo Jiaxin,Qi Jialong,Deng Wenxia,Hu Jialin,Hasan Muhammad Waqqas,Deng Fei,Zhou You,Song Zhengji,Deng Wei,Chen Wenjie
Immune checkpoint blockade therapy (iCBT) has revolutionized cancer treatment, however, there is a low response rate, especially in treating postsurgical reoccurring tumors. Vaccine based immunotherapy can sensitize iCBT, but its development was largely hindered by inefficient delivery and high requirements of storage. In this study, the vaccine loaded with immunostimulant was employed to improve iCBT-based adjuvant postsurgical therapy. A lyophilized, antigen E7 peptide and manganese ion (Mn 2+ ) co-delivered tumor vaccine was developed based on lipid nanoparticles (EM@LNP). The vaccination efficacy was examined in both prophylactic and therapeutic schemes in murine subcutaneous models, the synergetic effect of vaccination combined with anti-PD-1 therapy was further investigated in post-operative tumor model. EM@LNP vaccination elicited effective CD8 + T cell response through modulating tumor immunosuppressive microenvironment and conferring immune memory, demonstrating potent immunization in both preventive and therapeutic schemes. What’s more, EM@LNP vaccination orchestrated with iCBT, efficiently repressing tumor recurrence. Further mechanism studies using inhibitor for cells invitro and the investigation using STING −/− mice confirmed that the cGAS-STING signaling pathway activated by Mn 2+ is indispensable for LNP vaccination and the coordination with iCBT-based adjuvant immunotherapy. In summary, this study shows a lyophilized LNP vaccine could significantly amplify iCBT efficiency, providing a translational strategy of adjuvant immunotherapy for treating postsurgical tumor recurrence. Graphical abstract
研究领域:
肿瘤学
·
免疫学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Min Gao,Yue Song,Jing Liang,Tiantian Chen,Jiajia Luo,Panyu Du,Han Wang,Hongyu Leng,Zheng Wang,Xinlong Ma,Kai Wang,Yanjun Zhao
Concurrent induction of apoptosis and ferroptosis is promising in handling heterogenous cancers. We report a tailored polymeric micellar nanoplatform for the combinational anti-tumor therapy. Two stimuli-responsive amphiphlic block copolymers were synthesized, bearing three functional moieties, i.e. azobenzene, nitroimidazole and 3-fluorophenylboronic acid. Azobenzene could enhance the cellular uptake of micelles. Nitroimidazole and 3-fluorophenylboronic acid could deplete the reduced nicotinamide adenine dinucleotide phosphate (NADPH), glucose and adenosine triphosphate (ATP) under hypoxia, sensitizing ferroptotic and apoptotic cell death. The proof-of-concept was demonstrated in a triple-negative breast cancer cell line (MDA-MB-231). Irrespective of the free or encapsulated form, doxorubicin and auranofin showed a synergistic action, evidenced by a low combination index (< 1). The co-delivery micelles showed improved potency than the single drug-loaded micelles in terms of the biomarkers of apoptosis ( e.g. caspase 3/9, cytochrome c and ATP) and ferroptosis ( e.g. thioredoxin reductase, thioredoxin, glutathione, NADPH, malondialdehyde and lipid peroxides). The apoptosis and ferroptosis induction ability of cargo-free micelles was proved. The in vivo efficacy was verified in the MDA-MB 231 tumor-bearing nude mice model. The current work offers a promising strategy of combinational anti-tumor drug delivery for potent induction of ferroptosis and apoptosis via the sensitization effect of vehicle in the hypoxic tumor.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Lifeng Zhang,Shihua Luo,Rui Fan,Ruixi Li,Wenbin Li,Siting Chen,Fei Lan,Yitong Zhu,Tingting Ji,Ye Zhang,Ling Li
APE1, an essential enzyme for DNA repair, is overexpressed in various cancers and has been identified as a potential biomarker for cancer diagnosis. However, detecting APE1 at low expression levels in the early stage of cancer presents a significant obstacle. Here, we introduced a novel localized Cas12a-based cascade amplification (LCas12a-CA) method. This method confined both the terminal deoxynucleotidyl transferase and the crRNA/Cas12a complex onto the surfaces of gold nanoparticles (AuNPs). This confinement not only boosts the stability of the multiple enzymes but also induces a substrate channeling effect. As a result, it significantly accelerates the reaction rate and enhances the sensitivity of APE1 detection. Upon the addition of APE1, the AP sites within the APE1 primer can be recognized and cleaved by APE1, exposing the 3′-OH ends. In the presence of LCas12a-CA, polyA sequences are generated at 3′-OH ends with the help of TdT and dATP. The sequences directly enter the Cas12a system, activating the trans -cleavage activity of Cas12a, thereby cutting the reporters on the surface of AuNPs and releasing fluorescence. Our platform demonstrates a detection limit (LOD) as low as 2.51 × 10 −6 U/mL, which is more than 60 times lower than that of free Cas12a-CA. Furthermore, the LCas12a-CA exhibits enhanced resistance ability in extreme environments and has been proven effective for the detection of APE1 in clinical samples. Overall, this work offers a promising platform for robust biosensing in cancer diagnosis and prognosis.
研究领域:
分子生物学
·
癌症研究
·
生物技术
✓ 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）