JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Jingyao Li,Huixi Yi,Yuanyuan Fu,Jiani Zhuang,Zhixiong Zhan,Liyou Guo,Ji Zheng,Xiyong Yu,Dong-Yang Zhang
Hypoxia, which is a common characteristic of most solid tumors, not only contributes to the immunosuppressive nature of the tumor microenvironment (TME) but also reduces the efficacy of many oxygen-depleting therapies, including photodynamic therapy (PDT). In this study, we developed acidity-responsive biodegradable iridium-coordinated (IPC) nanodrugs consisting of iridium ions, the photosensitizer chlorin e6 (Ce6), and polyvinylpyrrolidone to potentiate the effects of PDT and immunotherapy by modulating the TME. IPC nanodrugs that accumulate at high levels in tumors catalyze excess hydrogen peroxide to produce oxygen while depleting glutathione levels within cancer cells; thus, the released Ce6 is more efficient at producing reactive oxygen species (ROS) in response to laser irradiation. In addition, IPC nanodrugs alleviate tumor hypoxia, induce more immunogenic cell death by amplifying PDT responses, and synergistically inhibit tumor growth by initiating robust antitumor immunity and reversing the immunosuppressive nature of the TME. As a result, IPC nanodrugs exert pronounced combined therapeutic effects in vitro and in vivo , without obvious toxic effects due to acidity-responsive degradation. These iridium-coordinated nanodrugs have the potential to modulate the TME, amplify the effects of PDT, and substantially inhibit tumors, and they are expected to provide novel ideas for combination therapy of hypoxic cancer.
研究领域:
癌症生物学
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纳米技术
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治疗学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2022
·Vol. 6
·期 11
·1522-1532
·
IF 8.683
Xuerui Zhu,Zhaoyou Chu,Benjin Chen,Qianqian Jin,Xuke Ma,Juan Yang,Yongxin Jiang,Wanni Wang,Zhengbao Zha,Haisheng Qian
Low concentrations of endogenous hydrogen peroxide (H2O2) and intrinsic oxidative stress defense system greatly limited the efficiency of Fenton and Fenton-like reactions driven by a single metal element. Moreover, the complex physiological environment and inherent self-healing function of tumors make it difficult for chemodynamic therapy (CDT) alone, driven by Fenton and Fenton-like reactions, to eliminate malignant tumors. Herein, a tumor microenvironment (TME) remodeling cobalt-stannous sulfide CoSnS2 (CSS) hollow nanocubes are presented for photothermal therapy (PTT)-improved CDT, in which two redox pairs (Co2+/Co3+ and Sn2+/Sn4+) are involved in catalyzing H2O2 to generate a large number of toxic hydroxyl radicals (˙OH) resulting in massive apoptosis of tumor cells. Importantly, two redox pairs (Co2+/Co3+ and Sn2+/Sn4+) promoted the depletion of glutathione (GSH), which reduced tumor antioxidant capacity and thus enhanced the CDT therapeutic impact of CDT. Furthermore, the CDT efficiency was greatly improved by the excellent photothermal effect (η = 47.23%). The combination of PTT and CDT achieved good therapeutic effects, which may provide a new perspective for the development of other anti-tumor strategies on the basis of improved CDT and modulation of TME.
研究领域:
纳米技术
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癌症治疗
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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
ACS Applied Materials & Interfaces
·
2023
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IF 9.5
Hongmei Kang,Lamei Chen,Qin Li,Huan Chen,Liangke Zhang
Due to the complexity of tumor pathogenesis and the heterogeneity of the tumor microenvironment (TME), it is difficult to obtain satisfactory efficacy with a single therapy. In this study, a hyaluronic acid (HA)-modified ruthenium nanoaggregate (RuNA) and glucose oxidase (GOD) -loaded manganese dioxide (MnO2) nanoflowers (MRG@HA) have been prepared. RuNA and MnO2 nanoflowers can generate O2 in TME, alleviating tumor tissue hypoxia. RuNA is a good photothermal agent for high-temperature ablation of solid tumors under infrared laser irradiation. GOD consumes glucose in the presence of O2 and converts it into glucuronic acid and hydrogen peroxide, reducing tumor nutrient supply while promoting Fenton-like reactions of MnO2 nanoflowers and RuNA to produce cytotoxic hydroxyl radicals. MRG@HA can also actively target tumor cells through the affinity of HA and CD44 receptor to improve the antitumor effect. In vitro and in vivo studies have confirmed the synergistic effect of MRG@HA with tumor photothermal/chemodynamic/starvation therapy, showing its great potential for clinical application in tumor therapy.
研究领域:
癌症治疗
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纳米医学
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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
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-14
·
IF 14.7
Wang Yuanlin,Han Yaqian,Yang Chenhui,Bai Tiancheng,Zhang Chenggang,Wang Zhaotong,Sun Ye,Hu Ying,Besenbacher Flemming,Chen Chunying,Yu Miao
The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag + release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.
研究领域:
肿瘤学
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免疫学
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微生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jiale Li,Bo Li,Feng Liu,Ming Deng,Ziying Zhang,Yutao Ran,Bing Wang
The significance of the tumor microenvironment (TME) in tumor initiation and progression is increasingly acknowledged. Conventional therapeutic approaches face limitations within the complex TME, including the restrictions imposed by hypoxia on photodynamic therapy (PDT) and the deficiency of endogenous H₂O₂ affecting chemodynamic therapy (CDT). In response to the TME's characteristics of high metabolism, hypoxia, and weak acidity, a multifunctional nanosystem MNPs/GOD@CS/IR820, which synergistically integrates CDT and PDT, has been developed. This system can actively accumulate at tumor sites under an external magnetic field and release active components in response to the weakly acidic TME. It mitigates the limitations imposed by hypoxia and endogenous H₂O₂ deficiency on PDT and CDT, respectively, thereby enabling synergistic treatment. Additionally, the system's multimodal imaging capabilities facilitate precise tumor localization and real-time, non-invasive in vivo assessment via fluorescence imaging and MRI. In vitro and in vivo evaluations demonstrate significant antitumor efficacy, effectively inhibiting tumor growth and improving survival rates. By comprehensively addressing the challenges posed by the complex TME and enhancing real-time monitoring capabilities, our nanosystem paves the way for personalized and precise cancer treatment. Statement of Significance This study introduces an innovative MNPs/GOD@CS/IR820 nanosystem that represents a significant advancement in cancer nanomedicine by addressing critical limitations of conventional photodynamic therapy (PDT), particularly in hypoxic tumor microenvironments. By synergistically integrating chemodynamic therapy (CDT) with PDT and incorporating MRI and fluorescence dual-modal imaging capabilities, this multifunctional platform offers enhanced therapeutic efficacy and real-time monitoring. The system's ability to generate oxygen in situ overcomes hypoxia-induced limitations, while its multimodal mechanism of action induces tumor cell apoptosis through multiple pathways. In vitro and in vivo studies demonstrate remarkable antitumor efficacy across diverse cancer types, significantly inhibiting tumor growth and improving survival rates. This comprehensive approach to cancer diagnosis and treatment not only advances precision medicine for targeted, multimodal cancer management but also provides a promising foundation for future clinical applications, potentially transforming cancer treatment strategies and improving patient outcomes.
研究领域:
纳米医学
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癌症生物学
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诊疗学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Shengsheng Mei,Shanshan Peng,Eu Gene Vong,Jinbiao Zhan
Background Clinical data indicate that a substantial portion of cancer patients, though eligible for immune checkpoint inhibitor (ICI) therapy, cannot fully benefit from ICI monotherapy due to the poor immunogenicity of tumors and lack of tumor-infiltrating lymphocytes within the ‘cold’ tumor microenvironment (TME). In addition to poor antibody penetrance into the TME, systemic delivery of ICIs is associated with immune-related adverse events (irAEs) among recipients, some of which are life-threatening. Oncolytic virotherapy is a potentially viable approach to improving the efficacy of ICI therapy because of their ability to selectively replicate and lyse tumor cells, release tumor-associated antigens (TAAs), induce inflammatory response and promote lymphocyte infiltration in tumors. Methods A recombinant oncolytic adenoviruses (OAd), denoted ZD55-aPD-L1 scFv, which carried the expression cassette for anti-PD-L1 scFv was constructed by molecular cloning. Western blot and ELISA assay were performed to detect aPD-L1 scFv expression. Flow cytometry were used to analyse PD-L1 expression and count tumor cells. Co-culture assay of human peripheral blood mononuclear cells (PBMCs) with tumor cells in vitro and triple-negative breast cancer (TNBC) MDA-MB-231 tumor-bearing model in vivo were evaluated the antitumor effects of recombinant oncolytic adenoviruses ZD55-aPD-L1 scFv. Results We found that cells infected with recombinant oncolytic adenovirus ZD55-aPD-L1 scFv can effectively express aPD-L1 scFv, which function similarly to its full-length anti-PD-L1 antibody. PBMCs have inherently very limited killing effect on tumor cells even with administration of anti-PD-L1 antibody as observed from our in vitro co-cultures. Treatment consisting of ZD55 alone or ZD55 combined with anti-PD-L1 antibody yielded mediocre antitumor efficacy in subsequent in vitro and in vivo investigations, but were all substantially surpassed by the synergistic antitumor effects observed with ZD55-aPD-L1 scFv treatment. We show that the concomitant direct oncolysis by the recombinant OAd and localized autocrine/paracrine interception of PD-1:PD-L1 checkpoint interaction mediated by ZD55-aPD-L1 scFv-infected cells is exceedingly superior to co-administration of ZD55 and anti-PD-L1 antibody in the human TNBC mice model. Conclusions Our results provided evidence for the development of novel strategies, in this case an anti-PD-L1 scFv-armed OAd, to bolster immune responses to ‘cold’ tumors and to improve therapeutic responsiveness to ICIs.
研究领域:
肿瘤学
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免疫疗法
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分子生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-14
·
IF 9.429
Deng Bo,Ma Bing,Ma Yingying,Cao Pei,Leng Xigang,Huang Pengyu,Zhao Yuanyuan,Ji Tianjiao,Lu Xueguang,Liu Lanxia
Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8 + and CD4 + T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect. Graphical Abstract
研究领域:
癌症治疗
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药物递送系统
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免疫疗法
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Yilu Zheng,Gareth R Williams,Ran Hu,Sen Tong,Jianxiang Xu,Tong Wang,Yanyan Zhang,Junzi Wu,Fan Li,Yingyu Cai,Li-Min Zhu
Background: The development of selective formulations able to target and kill tumor cells without the application of external energy has shown great promise for anti-tumor therapy.Methods: Here, we report a “nanobomb” that explosively increases Ca content within cells. It can selectively release Ca2+ and generate H2O2 in the tumor microenvironment (TME) by acid-triggered degradation of the two-layer protective shell (ie, unlocking the “double-lock”). This material, termed CaO2@ZIF8:CUR@PAA, comprises a CaO2 core coated with the ZIF-8 framework, which was then loaded with curcumin (CUR) and coated again with polyacrylic acid (PAA).Results: Under the slightly acidic conditions of the TME, the PAA shell (first lock) breaks down first exposing CaO2@ZIF8 and CUR inside the cell. Then, ZIF8 (second lock) is degraded in response to acid to deposit Ca2+, and H2O2. CUR can promote the release of Ca2+ from the endoplasmic reticulum to the cytoplasm, inhibit the outflow of Ca2+, and accumulates a large amount of Ca2+ intracellularly together with exogenous Ca2+ (calcium storms). The powerful calcium storm that causes mitochondrial dysfunction. The presence of a large amount of exogenous H2O2 causes further oxidative damage to tumor cell membranes and mitochondria where intracellular ROS production far exceeds clearance. CaO2@ZIF8:CUR@PAA NPs can induce cell S cycle arrest and apoptosis to inhibit tumor multiplication and growth. Oxidative damage-triggered immunogenic cell death (ICD) in turn leads to the polarization of macrophages to the M1 phenotype, inducing immunogenic cell death and inhibiting tumor cell proliferation and metastasis.Discussion: The acid two-step unlocking nanoplatform is a therapeutic modality that combines calcium storm and oxidative damage. The mode triggers apoptosis leading to ICD of tumor cells. The material induces cycle blockade during treatment to inhibit cell proliferation. Robust in vitro and in vivo data demonstrate the efficacy of this approach and CaO2@ZIF8:CUR@PAA as an anticancer platform, paving the way for nanomaterials in immune-triggered cancer therapy.Highlights: - A new calcium accumulation nanoplatform plays a role in activate antitumor immunity.- Double-locked structure slows down the premature decomposition of CaO2.- The platform allows Ca2+ and H2O2 to accumulate in tumor cells.- This leads to mitochondrial dysfunction, apoptosis, and M1 macrophage polarization.- Potent anti-tumor effects are seen both in vitro and in vivo.
研究领域:
癌症治疗
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纳米技术
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免疫学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 14
·期 2
·361-372
·
IF 7.79
Ruoxi Zhao,Rui Zhang,Lili Feng,Yushan Dong,Jialing Zhou,Songnan Qu,Shili Gai,Dan Yang,He Ding,Piaoping Yang
The construction of nanoplatforms with combined photothermal properties and cascading enzymatic activities has become an active area of anticancer research. However, the overheating of photothermal therapy (PTT) and the specific properties of tumor microenvironment (TME) greatly impaired the therapeutic efficiency. Herein, we rationally fabricated a virus-like SiOx/CeO2/VOx (SCV) nanoplatform for 1064 nm near-infrared (NIR) triggered mild-temperature PTT and nanozyme catalytic therapy. Firstly, the virus-like shape of SiOx/CeO2/VOx made it favorable for cell adhesion and improved its phagocytosis in cells, and the SCV generated an effective PTT effect upon 1064 nm laser irradiation. Particularly, the produced VO2+ in TME could be used as a heat shock protein inhibitor to inhibit the expression of heat shock protein 60 (HSP60) to enhance the PTT efficiency. Moreover, the SCV nanozyme exhibited obvious peroxidase-mimic (POD) catalytic activity, which could generate highly toxic free radical ions (˙OH) under acidic conditions. The mild-temperature heat and ˙OH produced by enzymatic catalysis effectively blocked the tumor growth, as verified firmly by in vitro and in vivo tests. Our designed virus-like SCV nanozyme with POD mimic enzyme activity and a mild photothermal effect may provide a new way of thinking about the combination therapy model.
研究领域:
纳米医学
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癌症治疗
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材料科学
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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
·
2022
·
IF 6.14
Weicai Wang,Xiaozu Chen,Junwei Li,Qiu Jin,Hyung Jong Jin,Xuemei Li
Nanotechnology provides more developments and challenges for cancer immunotherapy. Nanomaterial-mediated synergistic therapy, immunosuppressive adjustment of the tumor microenvironment (TME), and nanovaccine construction can promote cancer immunotherapy. Here, based on the biodegradable hollow manganese dioxide (H-MnO2) tumor-targeted drug delivery platform, we have developed a TME-responsive nanovaccine for synergistic cancer therapy. The nanoplatform significantly enhanced photodynamic therapy (PDT)-mediated immune response by improving the hypoxic tumor microenvironment and on-demand drug release. At the same time, it was supplemented with gene therapy and chemotherapy to achieve significant in vivo combined therapy benefits. Taking full advantage of the high reactivity to the hydrogen peroxide and weak acidity of the TME, H-MnO2 loaded with chemotherapy drug doxorubicin (DOX) and photosensitizer chlorin e6 (Ce6) not only provided the required oxygen for photodynamic therapy but also reduced the side effects of chemotherapy drugs on normal tissues. Moreover, the coating of nucleic acid on H-MnO2 solved the problem of biocompatibility of nanoparticles and ensured that they could be swallowed by cancer cells. The results revealed that through the controlled release of targeted drugs and combined therapy, the synergistic nanovaccine significantly inhibited tumor growth in mice, which is expected to achieve the treatment of primary tumors.
研究领域:
纳米技术
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癌症免疫治疗
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药物递送系统
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光动力疗法
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基因治疗
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化疗
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生物相容性
✓ 已验证
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Yupeng Guan,Chengyuan Xing,Tongyu Tong,Xinyi Zhang,Jun Li,Huikun Chen,Junfeng Zhu,Yang Kang,Jun Pang
Conventional chemotherapy efficacy is impeded by poor water solubility, inferior tissue targeting, and severe systemic toxic effect. Synergistic chemotherapy has become prominent with the stimulus–response drug delivery system (DDS) to treat solid malignancies. The most popularly employed responsive stimulus is reactive oxygen species (ROS), which is proven to primarily sensitize chemotherapy and enhance antitumor impact. In this study, we have successfully developed smart dual responsive nanocarriers with ROS self-amplification, particularly responding to disassemble under the high levels of ROS and esterase in the tumor microenvironment (TME) and to release docetaxel (DTX) efficiently. Additionally, we utilized palmitoyl ascorbate (PA) as a stabilizer by taking advantage of its amphiphilic structure. PA is also an excellent ROS generator that produces a large amount of hydrogen peroxide (H 2 O 2 ) in TME to achieve ROS self-amplification. Also, elevated levels of ROS could continue to activate ROS-sensitive thioketal and make the remaining nanocarriers disassemble for sustaining the release of chemotherapeutics, realizing a positive feedback loop for ROS generation and ROS amplification, as well as sensitizing chemotherapy efficacy. The smart dual responsive nanocarriers may serve as a promising and prospective strategy for treating prostate cancer and promoting synergistic cancer therapy.
研究领域:
纳米技术
·
癌症治疗
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药学科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Sa Wang,Shuqing Yang,Zhuolin Cui,Xueyan Liu,Yu Yang,Tao Wang,Wenjuan Ma,Yubin Zhou,Ruizheng Liang,Dan Yan,Huizhi Chen
Precise activation of therapeutic molecules in tumor tissues is the key step to ensure targeted antitumor performance and reduce adverse effects towards normal tissues and organs. Although the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), i.e., bioorthogonal chemistry, has been used for the rapid synthesis of anticancer drugs in cells, it remains a great challenge to realize precise in vivo drug synthesis in tumor sites for precise cancer treatment. In this work, we first report the in-situ activation of CuAl-layered double hydroxide (CuAl-LDH) nanosheets to realize Cu(I)-catalyzed bioorthogonal chemistry in vivo in tumor microenvironment (TME) for precise chemotherapy and chemodynamic therapy (CDT). The Cu(II) ions in the biocompatible CuAl-LDH nanosheets can be in-situ reduced to Cu(I) ions partially by the overexpressed glutathione in TME. The generated Cu(I) can serve as a catalyst to catalyze the CuAAC reaction between alkyne and azide in TME, thus realizing in vivo drug synthesis for precise chemotherapy. Meanwhile, the generated Cu(I) can catalyze the Fenton-like reaction to generate toxic hydroxyl radicals (⋅OH) from H 2 O 2 in TME for CDT. Therefore, CuAl-LDHs can be used for the targeted synergistic chemotherapy and CDT to achieve highly precise and efficient elimination of cancer cells in vitro and inhibition of tumors in vivo .
研究领域:
纳米技术
·
癌症治疗
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生物化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）