MATERIALS & DESIGN
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2026
·
IF 8.2
JunHui Wei,Tingting Wang,Jin Tao,Xuezhi Wang,Kangning Li,Junnan Kan,Yijie Lv,Kai Qi,Ailing Wang,Xianglin Li,Caixia Yang
Breast cancer remains a major clinical challenge due to its high incidence, tumor heterogeneity, hypoxia, and limited treatment specificity. In this study, we developed PMDH, a six-in-one integrated nanoplatform for targeted multimodal imaging and combined therapy. PMDH was constructed by sequentially coating a MnO 2 shell on PCN–224, loading doxorubicin (DOX), and conjugating hyaluronic acid (HA). The system features complementary tumor microenvironment (TME) responsive imaging modalities, including fluorescence imaging, magnetic resonance imaging, and photoacoustic imaging for precise diagnostics. Therapeutically, PMDH enables controlled DOX release for chemotherapy, self-enhanced photodynamic therapy (PDT) through intratumoral oxygen generation, and PDT-triggered immunotherapy. These integrated capabilities were comprehensively validated through in vitro and in vivo studies, underscoring PMDH’s potential as a versatile and precise platform for oncology treatment.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Hui Li,Jie Geng,Min Mu,Susu Xiao,Chenqian Feng,Lihua Zhou,Yuanxiang Wang,Wei Yu,Rangrang Fan,Bo Han,Gang Guo
The nanoheterojunction (NbCuF@MR) enables tumor-specific copper delivery. • Its TME-responsive design minimizes systemic toxicity and off-target effects. • The cascade amplifies oxidative stress to activate robust ICD. • Cuproptosis–immunomodulation–metabolic interference reprograms the TME. • It enhances immune infiltration, converting “cold” tumors into “hot” ones. Cuproptosis, an emerging copper-dependent programmed cell death, offers a promising strategy for cancer therapy. However, its clinical translation is hindered by non-targeted Cu release, causing systemic toxicity and limited efficacy. To overcome this, we developed a folate-targeted nanoheterojunction photosensitizer, NbCuF@MR, for tumor-specific copper delivery. This system responds to the tumor microenvironment to release active components, leading to mitochondrial copper accumulation, aggregation of lipoylated dihydrolipoamide S -acetyltransferase (DLAT), and induction of cuproptosis. Under 808 nm laser irradiation, Nb 2 C generates mild phototherapy effects that combine to enhance cuproptosis while producing ROS and O 2 . Furthermore, this cascade reactions promotes immunogenic cell death (ICD). Together with loaded R848 and MTX, the system reprograms the immunosuppressive tumor microenvironment through metabolic modulation and amplified cuproptosis, activating a robust antitumor immune response. This stimulates M1 macrophage polarization, DC maturation, and cytotoxic T-cell infiltration, effectively inhibiting both local and distant tumor growth and metastasis. In conclusion, this work offers an innovative strategy leveraging metabolic interference and enhanced cuproptosis to activate potent antitumor immunity. Download: Download high-res image (159KB) Download: Download full-size image
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高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2025
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IF 6.8
Yan Chen,Shuaiqi Feng,Lanjie Li,Guiqin Liu,Qingshan Ma,Zhifang Liu,Yanna Zhao,Qingpeng Wang
Grapefruit extracellular vesicle (GEVs) derived nanodrug Tf-GEVs@Pt(IV) loading novel three-functional platinum(IV) conjugates was developed, which was effective in modulating the inflammatory, fibrotic, and immunosuppressive tumor microenvironment (TME). The GEVs enhanced the penetration of Tf-GEVs@Pt(IV) into tumor tissues, while the transferrin (Tf) moiety further improved the tumor-targeting capabilities. The active ingredient, platinum(IV) conjugate, was released in a sustained manner within the TME, which was easily reduced to platinum(II), aspirin (ASP), and captopril (CTP) fragments. The platinum core caused significant DNA damage. The inflammatory TME was ameliorated by inhibiting COX-2 and reducing TNF-α and IL-6 through the synergistic actions of GEVs and ASP. Collagen fibrosis was disrupted by the CTP moiety, which downregulated TGF-β1, MMP2, and MMP9. Consequently, the immunologically ‘cold’ TME was transformed into a ‘hot’ state by inhibiting PD-L1 and activating cGAS/STING pathways. Then, the T-cell activation and macrophage polarization from the M2- to M1-phenotype were provoked in tumor tissues.
研究领域:
药理学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Journal of Magnesium and Alloys
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2026
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IF 13.8
Dong Li,Tong Zhang,Shaosheng Jia,Jianan Yu,Rongbang Sun,Bin Yin,Liguo Wang,Lingchuang Bai,Lan Chen,Shaokang Guan
Osteosarcoma (OS) poses a severe threat to human health, and the standard clinical treatment involves prosthetic replacement after surgical removal combined with radiotherapy and chemotherapy. However, the recurrence of residual tumors and extensive bone defects leads to a poor prognosis for patients. Zoledronic acid (ZA) is clinically used for tumor treatment and osteoclast inhibition. Nevertheless, intravenous infusion of ZA has poor targeting and significant toxicity to normal tissues. Biodegradable Mg alloys have excellent mechanical and biological compatibility, making them ideal for orthopedic implants. However, their application is limited due to poor corrosion resistance. This work applied a multi-composite layered double hydroxide (LDH)-ZA/PDA coating to the surface of ZE21C alloy. The composite coating adsorbed ZA in weakly alkaline or neutral conditions and released ZA under near-infrared (NIR) irradiation in the tumor microenvironment (TME). The stimuli-responsive release of ZA was confirmed to be related to the NIR-TME-triggered change in LDH interlayer spacing. In vitro and in vivo experiments showed that this multi-composite coating improved corrosion resistance, responded to TME and NIR stimuli to release ZA and reactive oxygen species, effectively targeting and killing tumor cells and osteoclasts through the AKT/GSK-3β signaling pathway. It also transformed OS from “cold tumors” into “hot tumors”, reactivated macrophage-mediated tumor immunity, and promoted osteogenesis. The chemo-thermal-therapeutic approach of the composite coating achieves a “three-birds-with-one-stone” effect. This study offers new insights into applying Mg alloys in prosthetic replacements after OS surgery.
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高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Zhe Tang,Wanru Luo,Mengmeng Xu,Yuan Liu,Qianqian Yu,LinGe Wang
This investigation addresses the pressing concern of tumor hypoxia, a phenomenon that significantly compromises the efficacy of photodynamic therapy (PDT) and chemotherapy in oncological treatment. This investigation presents a novel polymersome-based system, denoted as IR808/DOX@Psome/MnO2, which concurrently mitigates tumor hypoxia and enables triple-modal therapy, encompassing PDT, chemodynamic therapy (CDT), and chemotherapy, alongside dual-modality imaging capabilities for precise cancer treatment. Activated by the acidic and glutathione-rich tumor microenvironment (TME), MnO2 nanoenzymes first catalyze the conversion of H2O2 to O2, which reduces hypoxia and generates cytotoxic hydroxyl radicals (˙OH) and enhances CDT. The concurrent release of IR808 and doxorubicin (DOX) ensures spatiotemporally synchronized triple-modal therapy. It not only improves the efficacy of photodynamic therapy but also reverses chemotherapy resistance by inhibiting the drug efflux pathway. Furthermore, the system's activatable magnetic resonance imaging (MRI) and fluorescence imaging capabilities facilitate real-time visualization of tumor targeting and therapy progression, addressing a significant unmet need in precision oncology. The modular design of the platform permits customization with various therapeutic agents, thereby expanding its relevance to other diseases associated with hypoxia.
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PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Wei Chen,Wenyu Xie,Zhimin Gao,Chen Lin,Meiling Tan,Yaru Zhang,Zhiyao Hou
A core-shell-structured Cu 2 O@Mn 3 Cu 3 O 8 (CMCO) nanozyme is constructed to serve as a tumor microenvironment (TME)-activated copper ionophore to achieve safe and efficient cuproptosis. The Mn 3 Cu 3 O 8 shell not only prevents exposure of normal tissues to the Cu 2 O core to reduce systemic toxicity but also exhibits enhanced enzyme-mimicking activity owing to the better band continuity near the Fermi surface. The glutathione oxidase (GSHOx)-like activity of CMCO depletes glutathione (GSH), which diminishes the ability to chelate Cu ions, thereby exerting Cu toxicity and inducing cuproptosis in cancer cells. The catalase (CAT)-like activity catalyzes the overexpressed H 2 O 2 in the TME, thereby generating O 2 in the tricarboxylic acid (TCA) cycle to enhance cuproptosis. More importantly, the Fenton-like reaction based on the release of Mn ions and the inactivation of glutathione peroxidase 4 induced by the elimination of GSH results in ferroptosis, accompanied by the accumulation of lipid peroxidation and reactive oxygen species that can cleave stress-induced heat shock proteins to compromise their protective capacity of cancer cells and further sensitize cuproptosis. CMCO nanozymes are partially sulfurized by hydrogen sulfide in the colorectal TME, exhibiting excellent photothermal properties and enzyme-mimicking activity. The mild photothermal effect enhances the enzyme-mimicking activity of the CMCO nanozymes, thus inducing high-efficiency ferroptosis-boosted-cuproptosis.
研究领域:
纳米技术
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癌症生物学
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治疗学
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酶模拟
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光化学
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DOI
PubMed
高影响因子
Science Advances
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2020
·Vol. 6
·期 35
·
IF 13.117
Jingjing Liang,Huifang Wang,Wenxiu Ding,Jianxiang Huang,Xuefei Zhou,Huiyang Wang,Xue Dong,Guangyao Li,Enguo Chen,Fei Zhou,Hongjie Fan,Jingya Xia,Bo Shen,Da Cai,Pengxun Lan,Hanliang Jiang,Jun Ling,Zhen Cheng,Xiangrui Liu,Jihong Sun
Mounting evidence suggests that immunotherapies are a promising new class of anticancer therapies. However, the immunosuppressive tumor microenvironment (TME), poor immunogenicity, and off-target toxicity hinder the broader implementation of immunotherapies. Here, we describe a novel strategy combining chemotherapy and immunotherapy to modulate the TME by systemically and concurrently delivering the chemotherapeutic agent SN38 (7-ethyl-10-hydroxycamptothecin) and the STING agonist DMXAA (5,6-dimethylxanthenone-4-acetic acid) into tumors using triblock copolymer nanoparticles, named PS3D1@DMXAA, which enhances antigen cross-presentation and induces the conversion of the immunosuppressive TME to immunogenic TME through the newly found synergistic function between SN38 and STING activation. PS3D1@DMXAA thus shows potent therapeutic efficacy in three mice tumor models and elicits remarkable therapeutic benefit when combined with anti–PD-1 therapy. Our engineered nanosystem offers a rational design of an effective immunotherapy combination regimen to convert uninflamed “cold” tumors into “hot” tumors, addressing the major challenges immunotherapies faced.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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癌症研究
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DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Xiaozhao Wang,Jing Li,Zhengtao Luo,Zhimin Gao,Yongxin Huang,Jiamin Luo,Xinyi Wang,Yaru Zhang,Meiling Tan,Zhiyao Hou
Insufficient adenosine triphosphate (ATP) can reduce the synthesis of heat-stress-induced heat shock proteins (HSPs) to promote the efficiency of mild photothermal therapy (mPTT), thus the rational design of ATP-exhausted strategy based on nanotechnology is an effective approach to resuscitate mPTT. Herein, Nd 3+ doped nanocrystals (NaYF 4 :Nd@CaF 2 , Nd-NCs) modified hollow mesoporous manganese oxide (H-MnO x ) nanocomposite (H-MnO x @Nd-NCs, MN) is synthesized, and loaded with glucose transporters (GLUTs) inhibitor KL-11743, noted as MN-KL nanozyme. In tumor microenvironment (TME), MN-KL can react with overexpressed glutathione (GSH) to release KL-11743, which can suppress the synthesis of intracellular ATP at the source by blocking glucose uptake to inhibit HSPs expression, meanwhile, MN-KL catalyzes the production of ·O 2 − / 1 O 2 /·OH and lipid peroxidation (LPO) to cleave existing HSPs. Through a two-pronged strategy with ATP inhibition and oxide accumulation, reducing the level of HSPs can be guaranteed for achieving efficient mPTT in both subcutaneous and in situ tumor models in mice. During this process, Nd-NCs can absorb near-infrared light and convert it into heat, and the quenched fluorescence of Nd-NCs by H-MnO x can be recovered through GSH-triggered biodegradation in tumors, thus the modification of Nd-NCs not only provides photothermal effect but also enables MN to own TME-activated fluorescence imaging.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Hongjie Zhang,Jing Wang,Ruiying Wu,Benyan Zheng,Yanxiang Sang,Bibo Wang,Lei Song,Yuan Hu,Xiaopeng Ma
Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME-responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self-supply ROS-responsive cascade polyprodrug (PMTO) was designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO was degraded by endogenous ROS of the TME, another part of the polyprodrug backbone became cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy was further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrated remarkable antitumor efficacy, effectively addressing the limitations associated with MTO. This article is protected by copyright. All rights reserved
研究领域:
药理学
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纳米技术
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2023
·Vol. 12
·期 2
·e12310
·
IF 16
Xiaoning Wang,Ruoyi Wu,Peisong Zhai,Zheqi Liu,Ronghui Xia,Zhen Zhang,Xing Qin,Chuwen Li,Wantao Chen,Jiang Li,Jianjun Zhang
Tumour cells under hypoxia tend to modulate the number and contents of extracellular vesicles (EVs) to regulate the tumour microenvironment (TME) and thus promote tumour progression. However, the mechanism of how hypoxia influences the secretion of EVs remains to be elucidated. Here, we confirm the increased production of EVs in head and neck squamous cell carcinoma (HNSCC) cells under hypoxia, where endosome-derived EVs are the main subtype affected by insufficient O 2 . The accumulation of hypoxia-inducible factor-1α (HIF-1α) under hypoxia directly downregulates the expression of ATP6V1A, which is pivotal to maintain the homeostasis of lysosomes. Subsequently, impaired lysosomal degradation contributes to the reduced fusion of multivesicular bodies (MVBs) with lysosomes and enables the secretion of intraluminal vesicles (ILVs) as EVs. These findings establish a HIF-1α-regulated lysosomal dysfunction-EV release axis and provide an exquisite framework to better understand EV biogenesis.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Mengsi Zhang,Lu Wang,Hao Jin,Nan Zhao,Yi Liu,Shijie Lan,Shuwei Liu,Hao Zhang
Metal-phenolic networks (MPNs) have been conventionally formed by the coordination of metal ions and polyphenols, which can responsively release metal ions and polyphenols under the trigger of tumor microenvironment (TME), showing high potential in the field of antitumor. However, MPNs are mainly limited to multi-valency polyphenols, and the unavailability of single valency polyphenols greatly hinders their applications even though they have excellent antitumor activity . Herein, we demonstrate a FeOOH assisted preparation method for MPNs antitumor reagent by introducing the complexes of Fe 3+ , H 2 O and polyphenol (Fe(H 2 O) x -polyphenol y ) in the preparation process, which overcomes the shortage of single valency polyphenols. Taking apigenin (Ap) as an example, Fe(H 2 O) x -Ap y complexes are foremost formed, in which the Fe(H 2 O) x is capable of hydrolyzing to generate FeOOH, thus producing Fe 3+ -Ap networks-coated FeOOH nanoparticles ( [email protected] NPs). Under the stimulation of the TME, [email protected] NPs could release Fe 2+ and Ap, realizing ferroptosis and apoptosis for tumor combination therapy. In addition, FeOOH can shorten transverse relaxation time, acting as a T 2 -weighted magnetic resonance imaging contrast agent . The current efforts provide an alternative strategy for constructing MPNs by exploiting single valency polyphenols, which strengthens the potential of MPNs in antitumor applications.
研究领域:
纳米技术
·
癌症研究
·
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 10
·1321-1332
·
IF 4.521
Liu Heng,Liu Yu,Chu Chengchao,Tong Haipeng,Xue Wei,Wang Junqing,Liu Gang,Zhang Weiguo
The aberrant tumor microenvironment (TME) characterized by hypoxia and acidification is closely associated with tumor malignant phenotypes and treatment resistance. Designing biocompatible TME-responsive nanoagents via convenient fabrication procedures are of particular interest for
specific and effective tumor theranostics. In this work, bovine serum albumin stabilized manganese dioxide (MnO2) nanostructures (BMnNSs) were synthesized via an environmental-friendly and facile one-step biomineralization process at physiological temperature, which possess suitable
size, good water dispersibility, and excellent biocompatibility. Then, the photosensitizer 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH) was anchored onto BMnNSs with desirable loading efficiency, obtaining multifunctional BMnNSs-HPPH nanocomposites (BMnHNCs). The high reactivity of
MnO2 towards acidic pH/hydrogen peroxide (H2O2) was utilized to achieve TME responsive near-infrared fluorescence/magnetic resonance dual-modal imaging and improved photodynamic therapy. Owing to the efficient tumor accumulation of BMnHNCs mediated by the passive
targeting effect and generated oxygen in situ resulting from the reaction between MnO2 and endogenous H2O2 in tumor cells, the BMnHNCs exhibited remarkably enhanced tumor growth suppression compared with HPPH. Furthermore, tumor hypoxia and the vascular
endothelial growth factor expression were effectively attenuated by BMnHNCs. Notably, the BMnHNCs demonstrated no apparent in vivo toxicity upon intravenous administration. This biocompatible and biodegradable nanoformulation holds great potential for TME modulation and improved tumor
theranostics for clinical translation.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
材料科学
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DOI
高影响因子
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