JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Chenfeng Xu,Yu Sun,Yan Qi,Yulin Yu,Yangzhou He,Mei Hu,Qian Hu,Tingting Wu,Dan Zhang,Lihuan Shang,Huan Deng,Zhiping Zhang
Tumor heterogeneity is considered as one of main obstacles to limit the clinical application of stimuli-responsive nanocarriers . Multidrug resistance (MDR) is also a major challenge in cancer chemotherapy . Here, we developed a tumor redox heterogeneity-responsive prodrug with self-induced reactive oxygen species (ROS) amplification property for facilitating rapid drug release and overcoming MDR and lung metastasis . The prodrug can self-assemble into polymer micelles (PMs) with high drug loading content (~30%), good physiological stability, prolonged systemic circulation and enhanced tumor distribution. Moreover, the prodrug PMs can stimulate tumor-specific ROS signal amplification, which provided a replenishment of consumed ROS necessary for rapid and complete drug release. The elevated ROS could not only evoke the mitochondria-dependent apoptosis by caspase-9/3 activation, but also inhibit inherent and acquired drug resistance by altering expression of Bcl-2 protein family and by reducing mitochondria membrane potential (ΔΨm) and ATP level in cancer cells. As a result, the prodrug PMs showed enhanced efficacy for inhibiting tumor growth in S180 sarcoma tumor model and in drug-resistant tumor model MCF-7/ADR and preventing lung metastasis in 4T1 in situ breast cancer model. This novel approach reported here may provide a promising strategy in the design of stimuli-responsive nanocarriers for efficient therapy of multidrug resistant and metastatic tumor.
研究领域:
癌症治疗
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药学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2023
·Vol. 415
·期 12
·2249-2260
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IF 4.3
Guo Fei-Fei,Li Tong,Mu Xi-Ping,Zhang Xue,Xu Zhi-Hao,Sun Ping,Yu Ri-Lei,Xia Ya-Mu,Gao Wei-Wei
In this work, we design and synthesize 2,2′-(7,9-dimethyl-2,4,6,8-tetraoxo-6,7,8,9-tetrahydropyrimido[5,4-g]pteridine-1,3(2H,4H)-diyl)bis( N,N -bis(2-chloroethyl)acetamide) (PT-MCA) as a novel DNA intercalator and potential antitumor agent. Electrochemical analysis reveals the redox process of PT-MCA on the electrode surface. The bioelectrochemical sensors are obtained by modifying the surface of GCE with calf thymus DNA (ctDNA), poly (dG), poly (dA), and G-quadruplex, respectively. The DNA oxidative damage induced by PT-MCA is investigated by comparing the peak intensity change of dGuo and dAdo and monitoring the peaks of the oxidation products of guanine and/or adenine (8-oxoGua and/or 2,8-oxoAde). UV–vis absorption and fluorescence spectra and gel electrophoresis are further employed to understand the intercalation of PT-MCA into DNA base pairs. Moreover, PT-MCA is proved to exhibit stronger anti-proliferation activity than mitoxantrone against both 4T1 and B16-F10 cancer cells. At last, the oxidative damage of PT-MCA toward ctDNA is not interfered by the coexistence of ions and also can be detected in real serums. Graphical abstract
研究领域:
药物化学
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生物化学
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癌症研究
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电化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
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IF 13.3
Xiaodan Wei,Honglin Huang,Junhan Guo,Ningxi Li,Qingzhi Li,Tian Zhao,Geng Yang,Lulu Cai,Hong Yang,Chunhui Wu,Yiyao Liu
Reprogramming the immunologically “cold” environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator ( CuS/Z@M 4T1 ) is detailed by engineering a Zn 2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn 2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M 4T1 rapidly causes intracellular Zn 2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.
研究领域:
纳米技术
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癌症免疫治疗
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生物医学工程
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材料科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Jie Zhang,Liwen Wei,Xiaocao Ma,Jingguo Wang,Siping Liang,Kang Chen,Minhao Wu,Li Niu,Yuanqing Zhang
Metabolic dysregulation contributes not only to cancer development but also to a tumor immune microenvironment (TIME), which poses great challenges to chemo- and immunotherapy. Targeting metabolic reprogramming has recently emerged as a promising strategy for cancer treatment, but the lethality against solid tumors appears to be fairly restricted, partially due to the poor solubility of small molecule drugs. Herein, we construct a versatile biomimetic nanoplatform (referred to as HM-BPT) employing pH-sensitive tumor-tropism hybrid membrane-coated Manganese oxide (MnO 2 ) nanoparticles for the delivery of BPTES, a glutamine metabolism inhibitor. Basically, hybrid membranes consisting of mesenchymal stem cell membranes (MSCm) and pH-sensitive liposomes (pSL) enable the biomimetic nanoplatform to target TME and escape from endo/lysosomes after endocytosis . The results reveal that HM-BPT treatment leads to remarkable tumor inhibition, cytotoxic T lymphocyte (CTL) infiltration , as well as M1 phenotype repolarization and stimulator of IFN genes (STING) pathway activation in macrophages in a 4T1 xenograft model. Furthermore, glutathione (GSH) depletion and oxygen (O 2 ) supply synergistically ameliorate the immunosuppressive status of the TME, boosting potent antitumor immune responses. Overall, our study explores an integrated therapeutic platform for TME reprogramming and immune activation, offering tremendous promise for cancer combination therapy. Statement of significance Metabolic abnormalities and the tumor immune microenvironment (TIME) lead to hyporesponsiveness to conventional therapies, ultimately resulting in refractory malignancies. In the current work, a biomimetic nanoplatform (HM-BPT) was developed for TME metabolic reprogramming in favor of immunotherapy. Particularly, hybrid membrane camouflage endowed the nanoplatform with TME targeting, endo/lysosomal escape, and sensitive release properties. The impact of hybrid membrane fusion ratio on cellular uptake and cell viability was explored, yielding beneficial references for the future development of bioactive nanomaterials . Intravenous administration of HM-BPT substantially relieved tumor burden and restored innate and acquired immune activation in 4T1 xenograft models. In conclusion, the created HM-BPT system has the potential to be a promising nanoplatform for combining cancer therapies.
研究领域:
癌症治疗
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免疫学
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纳米技术
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Fangfang Yu,Tingya Wang,Yihan Wang,Tengfei Liu,Hongjie Xiong,Liu Liu,Jiang Xiao,Xiaohui Liu,Hui Jiang,Xuemei Wang
It is of great significance to design functional nanomaterials with specific response to tumor microenvironments (TMEs), so as to achieve accurate imaging and efficient treatment of tumor. In this work, a TME-activated biomimetic nanocomposite with dual imaging capabilities of turn-on fluorescence imaging and photothermal imaging was constructed for high-sensitivity sensing of glutathione (GSH) and self-enhanced photothermal/chemodynamic synergistic therapy. The nanocomposite was designed by loading nanozyme MnO 2 and luminol gold nanoclusters on ZIF-8 (Z-M-LA), which was then coated with 4T1 cell membrane (Z-M-LA@CM). The biomimetic membrane decoration was used to escape immune clearance and maintain good biocompatibility and targeting ability. The fluorescence of luminol gold nanoclusters quenched by MnO 2 can be recovered in vivo through MnO 2 degradation by GSH, which enables the TME-activated visualization of tumor. Simultaneously, MnO 2 shows peroxidase-like activity after being degraded by GSH and the released Mn 2+ can catalyze H 2 O 2 to generate abundant hydroxyl radicals (·OH) to realize self-enhanced photothermal/chemodynamic synergistic therapy. Furthermore, Z-M-LA@CM was also investigated to induce immune effect in vivo and it exhibited good pH-responsive degradation behavior, which could remain stable under alkaline conditions (pH = 7.4) and be degraded in acidic solutions (pH = 5.6). These properties make Z-M-LA@CM an appealing biodegradable nanotherapeutic agent for tumor precise diagnosis and therapy.
研究领域:
纳米技术
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生物医学工程
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癌症治疗
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材料科学
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生物化学
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诊疗一体化
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 44
·22615-22627
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IF 6.895
Ao Hu,Xiaobing Chen,Qunjie Bi,Yang Xiang,Rongrong Jin,Hua Ai,Yu Nie
Polarization regulation of tumor-association macrophages (TAMs) is a promising treatment method for tumors, but aiming at TAMs alone shows unsatisfactory therapeutic efficiency. Therefore, we designed a parallel and cascade control system for both macrophage polarization and tumor cell inhibition. The system is composed of cationic lipopeptides with an arginine-rich periphery (RLS) and anionic magnetic nanoparticles (MNPs) for fleet transfection of miR-125b. Based on the highly efficient magnetofection, miR-125b successfully shows a parallel effect on both M1, promoting polarization by targeting interferon regulatory factor 4 (IRF4) in macrophages, and tumor cell inhibition, by targeting ETS proto-oncogene 1 and cyclin- J. The cascading effect on M1-associated genes is upregulated by up to two orders of magnitude, while M2-associated genes are downregulated. Meanwhile, MNPs also have an effect on the TAM polarization and 4T1 tumor cell inhibition via inflammatory related gene expression and Fenton reaction. Further mimicking the co-culture of RAW264.7 and 4T1 cells in vitro confirmed the synergistic therapy effect. In the treatment of orthotopic breast cancer in mice, considerable M1 macrophage polarization was observed in the RM125b treated group, showing distinct tumor-suppressive effects, with a tumor weight reduction of 60% and tumor metastasis suppression of 50%.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
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IF 6.638
Jingdong Rao,Ling Mei,Ji Liu,Xian Tang,Sheng Yin,Chunyu Xia,Jiaojie Wei,Dandan Wan,Xuhui Wang,Yashi Wang,Man Li,Zhirong Zhang,Qin He
Autophagy plays a key role in the stress response of tumor cells, which contributes to cancer cell survival and resistance to chemotherapy by degrading cytoplasmic proteins to provide energy and clear the hazardous substances. Therefore, combined treatment of chemotherapeutics and autophagy inhibitors is thought to obtain a desirable antitumor effect. Nanoparticles (NPs) show potential in tumor-targeting drug delivery because of the enhanced permeability and retention (EPR) effect. However, NPs with fixed particle size cannot achieve optimal delivery effect. Herein, a strategy based on Cu (I)-catalyzed click chemistry-triggered aggregation of azide/alkyne-modified micelles was developed for the co-delivery of the chemotherapeutic drug doxorubicin (Dox) and the autophagy inhibitor wortmannin (Wtmn). In vitro experiments showed that the size of micelles increased in a time-dependent manner, which enhanced micelle accumulation in both B16F10 and 4 T1 cells. The fluorescence resonance energy transfer (FRET) experiment and biodistribution study further demonstrated that the aggregation of micelles through click cycloaddition significantly improved the accumulation of drug-loading micelles at the tumor region. Furthermore, the decreased amount of autophagosomes observed by transmission electron microscopy (TEM), the declined expression of LC3-II, and the increased level of p62 by western blotting and immunohistochemistry (IHC) confirmed the obvious inhibition of autophagy induced by Dox/Wtmn co-loaded size-adjustable micelles, which had a synergistic effect in cancer suppression. In addition, the co-loaded size-adjustable micelles showed outstanding cytotoxicity and antitumor effect. Therefore, this strategy effectively suppressed melanoma and breast cancer in mice. Statement of Significance The therapeutic effects of chemotherapy can be limited by autophagy; hence, combined use of autophagy inhibitors with chemotherapeutics achieves desirable anticancer efficacy. In the present study, we designed size-adjustable micelles by modifying the click reaction substrate azide group and the alkyne group on the surface of micelles, and subsequently, the autophagy inhibitor wortmannin and the chemotherapeutic drug doxorubicin were co-loaded. The micelles could aggregate by click reaction at the tumor site when the catalysts were intratumorally injected. The results showed that the size-adjustable micelles achieved efficient drug delivery, penetration, and retention in tumors; through the combined effect of wortmannin-mediated autophagy inhibition and doxorubicin-mediated cytotoxicity, this strategy exerted significant anticancer effect in melanoma and breast cancer treatment.
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Hui Qiao,Wenxia Zhang,Dongmei Zhang,Wenjun Yan,Jianguo Li,Yingqi Li
The redox homeostasis in tumor cells is an innate defense barrier for reactive oxygen species (ROS)-mediated tumor therapy. Herein, an intratumoral cascade-responsive multifunctional nanodiamond-based platform (NPCD) with a hydrodynamic diameter of 191 ± 5 nm triggering redox dyshomeostasis is fabricated by Cu2+-mediated coordination for polylysinated nanodiamond and doxorubicin (DOX) to achieve cancer-specific diagnosis and therapy. The NPCD nanoplatform enables precise tumor fluorescence localization and chemotherapy through a “turn on” effect due to being specifically activated by GSH to trigger DOX release at a low-pH tumor-specific environment instead of normal cells. Furthermore, NPCD realizes Cu+-based chemodynamic therapy (CDT) and induces GSH depletion by Cu2+ reduction to support CDT. These cause intracellular redox dyshomeostasis, making tumor cells more sensitive to the NPCD nanoparticles. Additionally, NPCD also possesses the intrinsic ability to reverse drug resistance. Of note, NPCD mainly accumulates in the tumor site in 4T1 tumor-bearing mice and enhances the efficacy of therapeutic interventions with negligible side effects. More interestingly, combined with programmed cell death ligand 1 antibody (anti-PD-L1) and imiquimod (R837), NPCD significantly suppresses distant tumor growth, indicating a good immune response. Therefore, this work opens perspectives for the further development of synergistic therapy through a Cu2+-mediated intratumoral cascade reaction.
研究领域:
纳米技术
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癌症治疗
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氧化还原生物学
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药物递送系统
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免疫肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Di Huang,Jing Zhu,Meng-Fan Xu,Jie Chen,Xing Gao,Long Zhao,Feng Ding,Cheng-Zhu Wu
Nano-drug carriers responsive to external stimuli have attracted greater scientific attention for the treatment of cancer. In this study, biodegradable DPA-DSDMA-PEG microgels were prepared as a drug delivery system via emulsion polymerization while using Doxorubicin (DOX) as the model drug. In this system, Bis(2-methacryloyloxyethyl) Disulfide (DSDMA) served as redox responsive cross-linker, 2-(Diisopropylamino) ethyl methacrylate (DPA) acted as monomers , and Poly (ethylene glycol) methyl ether methacrylate (PEG) was used as hydrophilic shells. The inclusion of PEG imparts excellent stability and good anti-fouling properties to the prepared microgel. Moreover, the microgels displayed dual pH/redox responsiveness, attributed to the pH sensitivity of DPA and the presence of disulfide bonds of DSDMA. Similarly, MTT assays showed that the DPA-DSDMA-PEG microgels displayed low cytotoxicity, even at concentrations of up to 100 μg/mL. Further, DOX@DPA-DSDMA-PEG inhibited the proliferation of 4T1 cells. In vivo studies showed that DOX@DPA-DSDMA-PEG microgels significantly enhanced the suppression of tumor growth. This work offers a promising strategy to design and develop dual-responsive and biocompatible nanomaterials for the treatment of cancer.
研究领域:
癌症治疗
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纳米技术
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药物递送系统
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
·
IF 5.4
Siao Yang,Xiaoxiao Hu,Zhengze Yong,Qingqing Dou,Cuilu Quan,Hong-Bo Cheng,Mo Zhang,Jing Wang
Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond , is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON’s large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON’s rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro . The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo , showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
免疫学
·
药学
✓ 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）