Small
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2021
·Vol. 17
·期 20
·2100130
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IF 13.281
Xuan Wang,Youbo Zhao,Lei Shi,Yan Hu,Guanbin Song,Kaiyong Cai,Menghuan Li,Zhong Luo
Nanocatalytic tumor therapy is an emerging antitumor option that employs catalytically-active inorganic nanostructures to produce tumor-damaging reactive oxygen species. However, initiation of nanocatalytic reactions in the tumor intracellular environment is a challenge due to the reliance on acidic pH. By exploiting the pH-selective multifaceted catalytic activities of Prussian blue-based nanomaterials (PBNM) as well as the hyperglycolysis characteristics of tumors, it is demonstrated that blocking the monocarboxylate transporter 4 (MCT4)-mediated lactate effusion in tumor cells can reverse the pH gradient across the tumor cell membrane and cause rapid intracellular acidification as well as neutralization of the extracellular compartment, thus creating vulnerabilities for PBNM-based nanocatalytic therapies in situ while suppressing tumor stemness/metastasis in vivo. For this purpose, MCT4-inhibiting siRNAs are incorporated into reactivity-switchable PBNM-based nanocatalysts to initiate hydroxyl radical production. Meanwhile, β-lapachone, a clinically-approved drug with H 2 O 2 -generating capabilities, is also integrated to sustain the nanocatalytic process. In contrast, the nanocatalyst shows no apparent toxicity to normal cells due to its catalase-like activities under neutral pH. This treatment strategy can inhibit tumor growth in mice at optimal safety as well as to suppress the cancer cell stemness and lung metastasis, suggesting the clinical translational potential of the findings.
研究领域:
肿瘤学
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纳米医学
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催化
·
生物化学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
·
IF 8.758
Yufei Cao,Mingsheng Liu,Ju Cheng,Juanjuan Yin,Congshu Huang,Haiyan Cui,Xiangdong Zhang,Guanghui Zhao
Nitric oxide (NO) gas therapy has aroused intense interest in recent years. l-Arginine (l-Arg) reacts with reactive oxygen species (ROS) in tumor cells to generate NO. This phenomenon represents an effective method for tumor therapy. However, endogenous ROS levels in most types of tumor cells cannot enable an effective reaction. β-Lapachone is generally used to increase H2O2, which can oxidize guanidine derivatives to form nitric oxide in tumor cells. In addition, based on the ferrocene (Fc)-catalyzed Fenton reaction, ·OH is generated from H2O2, and the ONOO– could be generated from an interaction between ·O2– (generated through the Haber–Weiss reaction) and NO. Arg-rich poly(ε-caprolactone) (PCL)-b-PArg, a macromolecular NO donor, was accurately synthesized to avoid premature l-Arg leakage during in vivo transport. In this design, the self-assembled PCL-b-PArg nanoparticles were dressed with the tumor-shreddable masking (PEG-b-PDMA, a negatively charged pH-sensitive hydrophilic diblock polymer), to prepare P-lapa-Fc nanoparticles and hide penetrative capability in the circulation. The experimental results confirmed that this synergistic therapy based on ROS and NO had a significant inhibitory effect on cancer cells, thereby providing new inspiration for NO gas treatment.
研究领域:
癌症治疗
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纳米医学
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药物化学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Hongxin Tan,Na Li,Sicheng Shu,Ziyan Fan,Jie Deng,Jingjing Wu,Xu Zhou,Qi Huang,Xi Cao
Cancer immunotherapy has garnered significant attention for its ability to reinstate immune responses to eliminate cancer effectively. Among immune cells, neutrophils play a dual-edged sword role in cancer, and the selective activation of beneficial neutrophil populations and targeted inhibition of tumor-promoting neutrophils have shown significant potential in cancer therapy. Here, we developed a neutrophil mimic nanovehicle (Neutrosome) capable of targeting colorectal cancer mitochondria (MNeutrosome), which consists of active neutrophil membranes hybridized with mitochondria-targeting liposome loaded with β-Lapachone (Liposome@Lapa), which is proposed to induce immunogenic cell death (ICD) and modulate the immune microenvironment. Our findings demonstrate that MNeutrosome@Lapa selectively accumulates in colorectal cancer mitochondria and activates quinone oxidoreductase-1 (NQO1), leading to robust reactive oxygen species (ROS) production and subsequent cancer cell apoptosis. Notably, the unloaded MNeutrosome was shown to reduce neutrophil infiltration into tumor tissue, whereas MNeutrosome@Lapa reprogrammed tumor-associated neutrophils (TANs) from a pro-tumor N2 phenotype to an anti-tumor N1 phenotype, further contributing to immune modulation. Overall, MNeutrosome@Lapa demonstrated excellent biocompatibility and significant therapeutic efficacy and represents a promising therapeutic platform for CRC treatment.
研究领域:
癌症免疫治疗
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纳米医学
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肿瘤微环境
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免疫学
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活性氧信号通路
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Shuai Wang,Yinghua Mao,Shu Rong,Guangquan Liu,Yongping Cao,Zhan Yang,Huanhuan Yu,Xinrui Zhang,Hongyue Fang,Zhipeng Cai,Yonghong Chen,Hao Huang,Hong Li
Chemodynamic therapy (CDT), employing metal ions to transform endogenous H2O2 into lethal hydroxyl radicals (•OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and β-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H2O2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H2O2 into •OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.
研究领域:
癌症研究
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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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诊疗学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Fang Liu,Yaru Li,Yao Li,Zheng Wang,Xin Li,Yancheng Liu,Yanjun Zhao
The clinical translation of the anticancer drug β -lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe 3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways ( e.g ., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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细胞死亡机制
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Minghao Sun,Weiwei Liu,Yuanyuan Ma,Pengfei Ni,Wenjing Yao,Yingjie Xu,Rui Bao,Jue Wang,Fei Xiong,Xihe Kuang,Teng Zhang,Xiaochen Zhang,Xikuang Yao,Shenghong Ju,Wenpei Fan
Chemodynamic therapy (CDT) efficacy in the tumor microenvironment (TME) remains compromised. Inspired by the potential of fever-like heat to activate a redox-favorable microenvironment, mild photothermal therapy (mPTT) is expected to sensitize tumors to CDT, turning “redox-cold” tumors into “redox-hot” ones. Herein, an injectable gel engine (LMFT@SG-R) is meticulously constructed based on the co-encapsulation of R848 and β-lapachone (LAP)-loaded metal–organic framework-199 (MOF-199) within a lipidic gel reservoir with the unique ability of thermally reversible sol–gel phase transformation. With mPTT reprogramming TME, the custom-designed LMFT@SG-R can realize systemic redox homeostasis remodeling through mPTT-activated chemodynamic immunotherapy (MPCIT). Once reaching the TME, LMFT@SG-R quickly hydrates into solid gel and subsequently undergoes gel-to-sol transformation under mild NIR laser irradiation, resulting in on-demand release of LMFT and R848 for controllable CDT and immunostimulation. LMFT undergoes stepwise degradation for sequential release of Fe 3+ , Cu 2+ and LAP, which can promote ROS cascade amplification owing to the upregulation of HSP70/NQO1 axis upon mild hyperthermia, resulting in robust ICD effects and T lymphocytes infiltrations together with R848. Notably, the controllable immunostimulation can facilitate robust abscopal effects and prominent suppression of distal tumors. The well-designed LMFT@SG-R may represent an updated CDT catalyst with the highly-integrated gel engine for chained-cooperative MPCIT.
研究领域:
癌症治疗
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生物医学工程
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免疫疗法
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化学生物学
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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）