JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Xiaorong Kou,Xue Wu,Tao He,Liping Bai,Xinchao Li,Rui Luo,Yangsong Xu,Yixi Wang,Meiling Shen,Changyang Gong,Qinjie Wu
Temporary amelioration of immunosuppression following extrinsic stress-induced immunogenic signal release provides opportunities for immunotherapy improvement. However, therapeutics that fail to translate local stimulatory clues into ongoing systemic antitumor responses would in turn hijack the alleviated immune status toward tolerance, instead of immunity. Here, we constructed a tumor-activated precise dual-metabolic nanomodulator (RAISE) that induced extensive tumor cell death while supporting DCs functions, thus synergistically turning over tolerogenic tumor control and skewing an antitumor immunity. Sequentially responsive to tumor-overexpressing enzymes and high intracellular GSH, RAISE disintegrated in a self-destructive manner, which facilitated drug release and produced immunogenic tumor cell death associated with immunosuppression relief. Then, the regression of tolerogenic metabolism by RAISE replenished intratumoral CD103 + DCs, which further amplified T cell activation by enhancing antigen cross-presentation. Moreover, the blockade of indoleamine 2,3-dioxygenase activity restored the sensitivity of tumors to T cell immunity. Consequently, the cascade of immune activation helped to escape from the fate of tolerance and evolved into durable immune memory. RAISE exhibited efficient tumor control, and when combined with anti-PD-1 immunotherapy, RAISE inhibited lung metastasis, generated systemic immune responses, and induced immune memory. Taken together, RAISE can be utilized to trigger long-term systemic antitumor immunity for improving tumor immunotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Analytical Science and Technology
·
2021
·Vol. 12
·期 1
·1-8
·
IF 2.769
Li Xiangfei,Qiao Juan,Sun Yongjun,Li Zhiwei,Qi Li
Precisely changing the optical properties of gold nanoclusters (AuNCs) with different ligands offers a promising prospect for highly sensitive and selective drug sensing. In this study, AuNCs were synthesized with d-tryptophan (d-Trp) and its derivatives as the ligands. Optical measurements showed that d-Trp@AuNCs produced higher fluorescence intensity and shorter fluorescence emission wavelength than the d-Trp-derivatives-ligands protected AuNCs, indicating that the ligand-shell rigidity and core-shell charge transfer affected their fluorescent properties. At the excitation wavelength of 370 nm, the emission wavelength of d-Trp@AuNCs was 460 nm. The fluorescence changes revealed the high selectivity of d-Trp@AuNCs for detecting folic acid due to the static quenching and inner filter effect. In the presence of folic acid, the fluorescence of d-Trp@AuNCs was remarkably quenched with good linearity ranging from 6.3-100.0 μM (R2 = 0.997) and a detection limit of 5.8 μM. The proposed assay was successfully utilized to determine the amount of folic acid in human urine with recoveries from 94.3 to 107.3%. This work shows the great potential of d-Trp@AuNCs for detecting folic acid in real bio-samples. It also presents an effective strategy for preparation of the AuNCs with enhanced fluorescence efficiency by regulating the rigidity of the ligands shell and the core-shell charge transfer.
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Qilin Li,Jia Liu,Huiling Fan,Lin Shi,Yan Deng,Lei Zhao,Mengxi Xiang,Yunruo Xu,Xulin Jiang,Guobin Wang,Lin Wang,Zheng Wang
Immunogenic chemotherapy (IC) is a type of chemotherapy where certain chemodrugs induce immunogenic cancer cell death (ICD), which in turn arouses T cell antitumor immunity. However, IC concurrently upregulates a key immune suppressor, indoleamine-2,3-dioxygenase (IDO), in both cancer cells and immune cells . IDO-mediated immunosuppression significantly offsets IC's therapeutic benefits in cancer patients , suggesting a necessity of combination with IDO inhibitors. Here, we report an enzyme-, pH-, and redox-triple-sensitive nanosystem using mesoporous silica nanoparticles (MSNs) as a core encapsulating doxorubicin (DOX, an immunogenic chemodrug); the core is coated with a shell ( β -CD-PEI/Ge1MT) for co-delivering 1-methyl-D-tryptophan (1 MT, an IDO inhibitor). By using these responsivenesses sequentially triggering the release of 1 MT into tumor extracellular compartment and DOX into intracellular endo/lysosomal compartment, this nanosystem ( [email protected] ) precisely delivers the drugs to their target cells residing in different compartments. Released 1 MT uptake by IDO-expressing dendritic cells (DCs) and cancer cells suppresses IDO activity, reducing immunosuppressive Tregs' presence; DOX unloaded within cancer cells induces ICD, promoting effector T-cell infiltration . In two preclinical cancer models, [email protected] potentiate both tumor local and systemic antitumor immunity, suppressing primary tumor growth by 78% with an 83% reduction in metastatic foci, as well as extending animal survival, thus strongly demonstrating [email protected] GMTMSNs' clinical translational potential.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2019
·
IF 3.206
Wenshuai Li,Saipeng Huang,Huiyun Wen,Yane Luo,Jiewei Cheng,Zhao Jia,Pu Han,Weiming Xue
Tryptophan (Trp) serves as an essential amino acid in protein and peptide metabolism of human body. Sensitive detection and quantification of Trp is imperative for the early diagnosis and prevention of Trp-associated disease. Herein, a highly sensitive and selective carbon quantum dot (Py-CDs) was fabricated and synthesized by a high-efficiency, one-pot hydrothermal route utilizing pyridine (Py) derivative 3-aminoisonicotinic acid. The biosensor with superior optical and biological characteristics exhibited excellent water solubility, good photostability, high biocompatibility and great cellular imaging capability. The Py-CDs exhibited high sensitivity and selectivity toward Trp with low detection limits of 5.7 nM. The mechanism research of high selectivity revealed the surface pyridine ring of Py-CDs served as an active site and formed the table nonfluorescence composite with tryptophan within just 15 s. Meanwhile, the biosensor has realized tryptophan detection in human serum samples with satisfactory accuracy and recovery. Furthermore, the biosensor was also extended to efficient detection of intracellular Trp, which illustrated its bright prospect and great potential in practical application of tryptophan associated disease prevention and early clinical diagnosis.
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2023
·
IF 17.4
Xinpei Liu,Xuan Yi,Jingyu Gu,Zhongfang Ji,Minqian Zhu,Mengling Shen,Yuanyuan Ren,Li Guo,Teng Liu,Nan Ding,Kai Yang
Glioblastoma with low cure and high recurrence is a serious threat to human health. Multifaceted synergy of intensive radiotherapy (RT) and systemic chemo-immunotherapy can develop a safe and effective treatment for glioblastoma. Herein, we dope bacterial membrane (BM) into the phospholipid layer of liposome to obtain BM-doping liposome (B-Lipo), which could be further loaded with 1-methyl- D -tryptophan (1-MT) and curcumin (Cur). Utilizing the BM doping, B-Lipo/1-MT&Cur could be effectively taken up by neutrophils, and cross the blood-brain barrier to brain tumor under the stimulation of up-regulated chemokines after RT. In the RT-treated glioblastoma, BM and the loaded drugs in B-Lipo/1-MT&Cur could reinforce RT-induced positive anti-tumor immune stimulation effect, such as immunogenic cell death and T cells infiltration, and reverse RT-caused negative immune stimulation effect including the polarization of macrophages and the expression of IDO, together realizing a potent systemic innate and adaptive anti-tumor immunity. More importantly, the combination of carbon ion RT and B-Lipo/1-MT&Cur could cure most of orthotopic glioblastoma-bearing mice and prevent its recurrence without causing any physiological and neuropsychiatric damage. Therefore, glioblastoma would be completely removed by intensive RT and the ingenious combination of local and systemic therapies, promoting the development of carbon ion RT and its combination therapy.
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Shikai Zhang,Qing Xu,Changbo Ji,Xiaoyu Han,Yang Zhou,Chao Liang,Linran Ma,Weijian Sun,Yanling Li,Zhengyou Yang,Fengchun Zhao,Yuan Tian
Small molecule-induced fermentation of the endophytic fungus Diaporthe sp. AC1 originated from Artemisia argyi was executed to investigate its secondary metabolites. It was fermented in a culture medium containing 5-hydroxytryptophan (5-HTP), 1-methyl-L-tryptophan (1-MT), and tryptamine (TA), respectively. The antibacterial activities of crude extracts against pathogenic bacteria and pathogenic fungi were determined by using the Oxford cup method, while the cytotoxicity of crude extracts against cancer cells was determined by using the MTT method. The results showed that the secondary metabolites of Diaporthe sp. AC1 induced by 1-MT exhibited optimal antibacterial activity and tumor cytotoxicity. The induction conditions of 1-MT were optimized, and the antibacterial activities and tumor cytotoxicity of crude extracts under different induction conditions were investigated. As indicated, the optimal moment for 1-MT addition was before inoculation and its optimal concentration was 0.25 mM. Under these conditions, Diaporthe sp. AC1 was fermented and approximately 12 g of crude extracts was obtained. The crude extracts were then separated and purified to acquire nine monomer compounds, including three new compounds ( 1 – 3 ) and six known compounds ( 4 – 9 ). The antibacterial activities of the compounds against pathogenic bacteria and pathogenic fungi were investigated by using the microdilution method, while their cytotoxicity against cancer cells was analyzed by using the MTT method. The results demonstrated that Compound 1 exhibited moderate antibacterial activities against Verticillium dahlia , Fusarium graminearum, and Botrytis cinerea , as well as a low inhibitory activity against Listeria monocytogenes . Nevertheless, Compound 1 showed significant cytotoxicity against five cancer cells, with IC 50 ranging from 12.26 to 52.52 μM. Compounds 2 and 3 exhibited negligible biological activity, while other compounds showed detectable inhibitory activities against pathogenic bacteria and cancer cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Ping Huang,Yao Yang,Wenyan Wang,Zimu Li,Nansha Gao,Hongzhong Chen,Xiaowei Zeng
Insufficient immune stimulation and stubborn immune resistance are the critical factors limiting tumor immunotherapy. Here, we report a multifunctional nanoprodrug platform with self-driven indoximod (IND) release and oxidative stress amplification. The aim is to awaken immune responses and block the indoleamine 2,3-dioxygenase (IDO) pathway through a combination of ferroptosis , photothermal therapy, and immunotherapy. This nanosystem improved the delivery efficiency of IND due to click chemistry linked ROS responsive prodrug and self-driven drug release. Meanwhile, the tactic of simultaneously increasing ROS and eliminating GSH amplified oxidative stress and strengthened ferroptosis, which further enhanced immunogenicity along with polydopamine-based photothermal therapy. IDO immunization combined with ferroptosis as well as photothermal therapy not only stimulated immune response, but also reversed immune suppression with enhanced immune memory . Therefore, primary tumor, distant tumor, and cancer metastasis were inhibited. This study provides a perspective on immunotherapeutics for cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Li Liao,Yufei Liu,Xianhai Li,Zewei Jiang,Zhijie Jiang,Jing Yao
Effective tumor immunotherapy is hindered by an immunosuppressive tumor microenvironment (TME), especially in triple-negative breast cancer. Though phototherapy could induce immunogenic cell death (ICD) to increase antitumor immunity, the simultaneous upregulation of indoleamine 2,3-dioxygenase (IDO) induces the negative immunomodulatory effect termed as the “immune-metabolism” loop to compromise immunotherapeutic efficacy. Herein, we developed IMMGP consisting of biomimetic IND-Mn@PM (IDP) and ICG-MnO2@PM (IMP), which combines the phototherapy-induced ICD and metabolic reprogramming to solve the dilemma. During the light-on phase, IMP effectively kills cancer cells with potent photodynamic ROS generation with the assistance of MnO2-produced oxygen and induces ICD to reverse the immunosuppressive TME. In the light-off phase, Mn2+ (from IDP and MnO2-based redox reaction) elicits a Fenton-like reaction to relay ROS generation, which is further orchestrated with continuous exhaustion of intratumoral GSH by the conversion of Mn3+ to Mn2+, and promotes dendritic cell maturation. Moreover, the released indoximod (IND) downregulated IDO to inhibit kynurenine metabolism, which reinvigorates T cell-mediated antitumor immunity. Collectively, IMMGP amplifies the immune response by breaking the “immune-metabolism” loop and sustaining the “immunologically hot” state after phototherapy, thus leading to nearly complete tumor inhibition (94.25%). Thus, IMMGP-mediated dual-phase photodynamic immunotherapy offers a novel approach in cancer nanomedicine.
✓ 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）