CHEMISTRY-A EUROPEAN JOURNAL
·
2025
·
IF 3.7
Gankun Yuan,Ruyue Yang,Wenjing Wen,Zhaoyi Wei,Meiru Song,Lingyang Zhang,Kun Hou,Gaofeng Liang
Graphical Da-CD@CET@CQ NPs can accurately target tumor cells, and the ER-targeting photosensitizer CET can be used as an ICD inducer for amplifying the ICD effect. Meanwhile, the ER PDT was further strengthened by autophagy inhibition, which can achieve more effective autophagy-regulated photodynamic synergistic immunotherapy for triple-negative breast cancer. Activating immunogenic cell death (ICD) represents a promising therapeutic strategy for tumor immunotherapy. However, photodynamic therapy (PDT)-mediated ICD effect is severely limited due to the extremely short half-life and limited diffusion radius of reactive oxygen species (ROS), hindering effective endoplasmic reticulum (ER) stress induction. In addition, targeted therapy of triple-negative breast cancer (TNBC) remains hugely challenging due to the lack of expression of multiple receptors. Herein, we constructed a hierarchical targeting and controllable intelligent nanodelivery material Da-CD@CET@CQ based on poly- β -cyclodextrin with remarkable solubility and stability, loaded with a novel photosensitized ICD inducer, CET, and autophagy inhibitor chloroquine (CQ). Excitingly, Da-CD@CET@CQ NPs can accurately recognize TNBC tumor cells under the mediation of SRC protein. Moreover, CET could achieve observable enrichment in the ER and amplify the ICD effect by in situ ER PDT, which is further strengthened by the autophagy inhibition caused by CQ. All results show that Da-CD@CET@CQ NPs exhibited excellent targeting ability to tumor cells and ER and effectively enhanced synergistic immunotherapy of in situ ER PDT combined with autophagy inhibition, which significantly inhibited tumor growth and metastasis. Overall, our study provides a novel strategy and meaningful guideline for targeted-PDT-synergistic immunotherapy of TNBC.
研究领域:
肿瘤学
·
免疫学
·
药剂学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Fei Kong,Zhiqiang Zeng,Xiaorong Zhu,Qingqing Wu,Lu Zhou,Changwei Dou,Zhongbo Xie,Lidong Cao
The combination of photodynamic therapy and immunotherapy has emerged as a safe and effective cancer treatment strategy. However, traditional photodynamic therapy and precision anti-tumor immunotherapy still face challenges, such as weak light source penetration, poor targeting specificity, low response rates and immune-related adverse effects. Herein, a smart polymer nano-immunomodulator (SPNI) that can respond to the tumor microenvironment for precise photodynamic immunotherapy of cancer is reported. This SPNI is self-assembled from pH and glutathione (GSH) bi-responsive amphiphilic polymers, simultaneously loaded with photosensitive materials and oxygen-carrying molecules, subsequently is wrapped by hepatocellular carcinoma (HCC) cell membrane using a simple coextrusion method to generate biomimetic nanoparticles. Upon reaching the tumor site, the SPNI degrades in the tumor microenvironment, effectively releasing photosensitive substances with chemophotodynamic effects to directly eliminate tumors without an external light source. Additionally, the immunosuppressant blocks PD-1/PD-L1 signaling pathways to enhance the body’s endogenous anti-tumor immune response, inhibiting tumor growth and metastasis. Furthermore, the incorporated immunosuppressant effectively blocks PD-1/PD-L1 signaling pathways, thereby potentiating endogenous anti-tumor immune responses to suppress both primary tumor growth and metastatic progression. This innovative combination of tumor microenvironment-responsive photodynamic therapy and checkpoint blockade immunotherapy demonstrates remarkable efficacy in anti-HCC treatment and shows substantial potential for clinical translation. The SPNI platform represents a significant advancement in precision cancer therapy by simultaneously addressing multiple limitations of current treatment modalities.
研究领域:
医学
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生物材料学
·
肿瘤学
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产品关联
DOI
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Chengxi Li,Can Yang,Tiantian Jiang,Zheming Song,Danling Cheng,Jingchao Li,Yong Han,Ting Su
Tumor microenvironment (TME) offers a promising approach to enhancing cancer therapy by altering the conditions that support tumor growth and immune evasion. However, tumors are highly heterogeneous, and the TME can vary greatly even within different regions of the same tumor. Moreover, tumors can evolve resistance mechanisms that limit the effectiveness of therapies. In this paper, we have designed a multifunctional nanoparticle named Lip-Ce6-MnO2-TPZ, making sonodynamic therapy (SDT), chemodynamic therapy (CDT), and hypoxia-activated prodrugs work synergistically to maximize cancer treatment efficacy. The innovative Lip-Ce6-MnO2-TPZ nanoparticle was constructed by loading Ce6, MnO2, and hypoxia responsive drug tirapazamine (TPZ) together into a cytotoxic reactive oxygen species (ROS) responsive nanocarrier. Upon ultrasound (US) irradiation, ROS generated by Ce6 could not only induce cell apoptosis but also accelerate the disassembly of the nanoparticle for enhancing the release of TPZ and MnO2. As a result, SDT consumed oxygen leading to the aggravation of hypoxia condition in the tumor site for TPZ activation and DNA damage in tumor cells. Meanwhile, the MnO2 was reduced to Mn2+ by GSH and caused antioxidant depletion. Mn2+ triggered CDT through a Fenton-like reaction by converting H2O2 to highly toxic •OH. Taking together, the Lip-Ce6-MnO2-TPZ platform could induce the generation of excess ROS combined with antioxidants depletion, resulting in oxidative stress and aberrant redox homeostasis of TME. This strategy has brought forward the idea of inducing cancer cell death by synergistically working SDT, CDT, and hypoxia-activated prodrugs together to maximize the therapeutic efficacy in cancer treatment.
研究领域:
肿瘤学
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纳米医学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Zhexu Wang,Yanfang Cheng,Bowen Liu,Baohua Zhu,Mingjun Xuan
Photodynamic therapy (PDT) utilizes photosensitizers to generate reactive oxygen species (ROS) for tumor treatment. However, its efficacy is often hindered by the limited tissue penetration and inefficient photosensitizer delivery. The development of upconversion nanoparticles (UCNPs) offers a promising solution to these challenges by converting near-infrared (NIR) light into visible emissions, thereby enabling deeper tissue activation. Herein, we present a urease-powered Janus UCNP nanomotor that combines active photosensitizer delivery with NIR-activated PDT. The nanomotors features a UCNP core and a Janus mesoporous silica shell loaded with chlorin e6 (Ce6), which is further activated by UCNP-emitted visible light under 980 nm NIR irradiation. Through urea decomposition catalyzed by urease, these Janus nanomotors gain self-propulsion capabilities, enhancing cellular uptake and facilitating deep tumor tissue penetration. This active motion markedly improves Ce6 delivery efficiency and promotes ROS generation, thereby enhancing the therapeutic efficacy of PDT. The enzyme-powered Janus UCNP nanomotors present a precise and minimally invasive platform for effective and targeted cancer therapy.
研究领域:
生物医学工程
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纳米医学
·
癌症治疗
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产品关联
DOI
高影响因子
NANOTECHNOLOGY
·
2025
·Vol. 36
·期 30
·305101
·
IF 2.8
Gaojian Liu,Wenjing Wen,Xuan Zhao,Yanan Jing,Hao Li,Xulong Fan,ZiXuan Huang,Gaofeng Liang
Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol–maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional ‘natural’ nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Congyang Mao,Wanyu Jin,Yiming Xiang,Yizhou Zhu,Jun Wu,Xiangmei Liu,Shuilin Wu,Wei Qiao,Kenneth M. C. Cheung,Kelvin Wai Kwok Yeung
Reactive oxygen species (ROS) are a promising alternative bactericide. However, it is questioned that bacteria can potentially develop resistance to ROS, similar to their resistance against antibiotics and silver. Herein, it is reported that Gram-negative bacteria, including Pseudomonas aeruginosa , Escherichia coli , and Klebsiella pneumoniae , develop resistance to ROS after six repeated exposures. Notably, ROS minimum inhibitory concentration of Pseudomonas aeruginosa significantly increases to 256-fold after ten passages. The resistance mechanism predominantly originates from the intensified biosynthesis of the highly reductive hydrogen sulfide (H 2 S) and pyoverdine (PVD) siderophores, effectively neutralizing ROS. Simultaneously, PVD transports Fe 3+ from the extracellular space into the bacteria, releasing H 2 S bound to Fe 3+ and enhancing ROS scavenging. Additionally, the enhanced outer membrane (OM) biogenesis establishes a robust OM barrier, impeding ROS penetration. The acquired resistance to ROS can be significantly reduced by incorporating additional Fe 3+ into the culture medium or disrupting the H 2 S biosynthetic gene. These observations suggest that careful consideration is required when utilizing ROS against Gram-negative bacteria. It is anticipated that understanding this resistance mechanism can inform the development of future antimicrobial agents, particularly for Gram-negative bacteria.
研究领域:
微生物学
·
分子生物学
·
感染与免疫
·
抗菌药物研究
·
细菌耐药机制
·
氧化应激
·
代谢调控
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 33
·15508-15518
·
IF 6.97
Xunan Jing,Yanzi Xu,Daomeng Liu,Youshen Wu,Na Zhou,Daquan Wang,Kai Yan,Lingjie Meng
Although the collaborative therapy of chemotherapy (CT) and photodynamic therapy (PDT) is much more efficient for tumor treatment than monotherapies, premature leakage of drugs from nanocarriers and hypoxia in the tumor microenvironment (TME) result in systemic toxicity and suboptimal therapy efficiency. To overcome these limitations, we developed an intelligent nanoflower composite (termed FHCPC@MnO2) by coating functionalized polyphosphazene on superparamagnetic Fe3O4 nanoclusters and then growing MnO2 nanosheets as an outer shell. The FHCPC@MnO2 nanoflowers with multistage H2O2/pH/GSH-responsive properties could fully exploit TME characteristics, including supernormal glutathione (GSH) levels, low pH and high H2O2, to realize the specific release of drugs in tumors and maximum synergetic therapeutic effects. The MnO2 nanosheets can elevate O2 concentration by catalytic decomposition of H2O2 and can be simultaneously reduced to Mn2+ by overexpressed GSH in the acidic TME. Meanwhile, the inner polyphosphazene containing (bis-(4-hydroxyphenyl)-disulfide) is GSH- and pH-sensitively biodegradable to release the anticancer drug curcumin (CUR) and photosensitizer chlorin e6 (Ce6) in the TME. Therefore, the “triple-responsive” and synergetic strategy simultaneously endows the nanoflowers with specific drug release, relieving hypoxia and the antioxidant capability of the tumor and achieving significant optimization of CT and PDT. In addition, the resulting Mn2+ ions and Fe3O4 core enable in vivo T1/T2 magnetic resonance imaging (MRI), while the released Ce6 can simultaneously provide a fluorescence imaging (FL) function. Unsurprisingly, the intelligent nanoflowers exhibited remarkable multimodal theranostic performance both in vitro and in vivo, suggesting their great potential for precision medicine.
研究领域:
癌症治疗
·
纳米医学
·
材料科学
·
生物医学工程
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 39
·18426-18435
·
IF 6.97
Meng Duan,Fangfang Xia,Tianliang Li,Joseph G. Shapter,Sheng Yang,Yongying Li,Guo Gao,Daxiang Cui
This work explored the application of matrix metalloproteinase 2-targeted superparamagnetic nanoprobes for magnetic resonance imaging (MRI), near infrared (NIR) fluorescence imaging and photodynamic therapy of tumors. PEG, PAMAM (G5) and matrix metalloproteinase 2 (MMP2) were attached to the surface of carboxylated Fe3O4 nanoparticles (NPs) using a chemical coupling method and then finally loaded with the photosensitizer chlorin e6 (Ce6). In vitro and in vivo experiments demonstrated that the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes exhibited excellent stability, precise tumor targeting and biocompatibility. Furthermore, the fluorescence properties of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes were analogous to Ce6 and could be employed for fluorescence imaging. Meanwhile, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes have also been shown to be effective as contrast agents for T2-weighted MRI. The target molecule MMP2 enhanced the tumor targeting ability of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes. Additionally, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes significantly inhibited tumor growth compared with PBS and free Ce6. This work will inspire greater enthusiasm for the construction of multifunctional magnetic nanoplatforms for biomedical applications.
研究领域:
生物医学工程
·
材料科学
·
纳米技术
·
癌症研究
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qian Wang,Mingjie Chen,Junwei Yao,Gang Zhou,Dandan Zhang,Qingshan Shi,Qianwen Mai,Xiaobao Xie
The increasing prevalence of drug-resistant bacteria and the ecological burden of synthetic antimicrobials demand sustainable biomaterials with superior antibacterial properties. Natural lignin, an amorphous polymer, presents considerable potential as a structural building block for sustainable biomaterial. Herein, inspired by antimicrobial photodynamic inactivation, kraft lignin was first reacted with formaldehyde and ethylenediamine to synthesize aminated lignin, the aminated lignin was further reacted with acetic anhydride, resulting in modified lignin. Thereafter, the modified lignin functions as a carrier, encapsulating the hydrophobic photosensitizer chlorin e6 to improve its dispersibility and aqueous solubility. Chitosan was further utilized to coat the nanoparticles, improving bacterial uptake, ultimately obtaining the desired final nanospheres (CS-ML-Ce6). Upon laser irradiation, CS-ML-Ce6 achieved >99.99 % bactericidal efficiency against methicillin-resistant Staphylococcus aureus . Additionally, it demonstrated a minimum inhibitory concentration of modified lignin of 67.71 μg/mL when exposed to light. It could result in membrane disruption and intracellular component leaking, while bacterial adsorption increased to 47.36 %. The dead/live rate of CS-ML-Ce6 against drug-resistant pathogens was almost 8-fold to modified lignin control. Concurrently, hemolysis assays with rabbit red blood cells confirmed exceptional biocompatibility, with hemolysis rates maintained below 5 % even at 6 × MIC concentrations. Considerable reactive oxygen species scavenging effectiveness at both the solution and cellular levels was also observed of CS-ML- Ce6, this dual-function approach uniquely combines light-activated bactericidal properties and dark-phase antioxidant repair. Utilizing lignin, an industrial byproduct, provides an efficient and promising antimicrobial alternative to prevent overuse of antibiotics and has significant potential for human healthcare.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
微生物学
·
光动力疗法
·
高分子科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Guoqing Cui,Ziyao Lu,Jiangnan Shi,Xinyu He,Yuwei Wang,Hui Chen,Zixiang Jia,Junchang Chen,Jie Han,Hui He,Zhengqing Guo
Overcoming resistance to radiotherapy remains a significant challenge in breast cancer management. A one-step coordinated synthesis of BODIPY -integrated photodynamic nanozymes ( FZBNPs ) that facilitate an orthogonal catalytic cascade for radiotherapy potentiation is presented. The engineered FZBNPs simultaneously alleviate tumor hypoxia through catalase-mimetic oxygen (O 2 ) generation and amplify reactive oxygen species (ROS) production via peroxidase-like activity, synergizing with BODIPY -mediated singlet oxygen ( 1 O 2 ) generation under 660 nm light irradiation. Crucially, FZBNPs deplete intracellular glutathione (GSH) and trigger ferroptosis through lipid peroxidation (LPO) accumulation, directly countering radiotherapy resistance. In vivo validation revealed that the FZBNPs -driven multi-enzymatic cascades achieved near-complete tumor ablation in breast cancer models during radiotherapy. This work establishes a therapeutic paradigm that integrates oxygen modulation, ROS amplification, redox homeostasis disruption, and ferroptosis induction, offering a conceptual basis for the application of enzyme-mimetic nanoplatforms in precision radiation oncology.
研究领域:
纳米医学
·
放射肿瘤学
·
癌症治疗
·
酶模拟
·
光动力治疗
·
活性氧生物学
·
铁死亡研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yilin Wang,Wenting Cheng,Yang Chen,Hailong Tian,Canhua Huang,Ka Li
Cancer stemness in colorectal cancer (CRC) drives immune evasion and fosters an immunosuppressive tumor microenvironment (TME), limiting the efficacy of immunotherapy. To counteract this stemness-driven immune evasion, we developed a hyaluronic acid (HA) surface-modified dual-targeting nanoplatform (HA/pCe6-Ato NPs) that induces both endoplasmic reticulum stress and mitochondrial dysfunction. HA functionalization facilitates tumor-specific targeting via CD44 receptor-mediated endocytosis. The nanoplatform incorporates an ER-targeting photosensitizer, pCe6, synthesized by conjugating Chlorin e6 with p-Toluenesulfonamide, and the mitochondrial respiratory chain inhibitor atovaquone (Ato), which self-assembles into nanoparticles. Upon activation, HA/pCe6-Ato NPs induce ER stress and mitochondrial dysfunction, disrupting cancer stemness and reprogramming the immunosuppressive TME. Preclinical evaluations showed that HA/pCe6-Ato NPs promote apoptosis and accelerate reactive oxygen species production in cancer stem-like cells (CSCs), while reducing immunosuppressive factor secretion and enhancing immune effector cell infiltration. These effects synergistically enhance the efficacy of immunotherapy, achieving superior tumor inhibition compared with conventional monotherapies. Collectively, HA/pCe6-Ato NPs highlight the potential of organelle-targeting strategies to dismantle cancer resilience mechanisms, providing a foundation for dual-targeting nanomedicines to overcome resistance and enhance immunotherapy in CRC.
研究领域:
纳米医学
·
癌症免疫治疗
·
分子靶向治疗
·
肿瘤生物学
·
活性氧信号通路
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhe Zhang,Qitai Chen,Rujia Zheng,Zhenduo Shao,Xiaobao Wei,Xuanhao Gu,Yi Zang,Xishan Yang,Jiangchao Wu,Mengyao Dai,Wanyue Cao,Yangyang Wang,Yize Zhang,Chengyang Hu,Cao Chen,Linquan Wu,Tingbo Liang,Qi Zhang
Gemcitabine-based chemotherapy remains a cornerstone in pancreatic cancer treatment, yet its efficacy is hindered by poor bioavailability and adaptive resistance mechanisms, such as autophagy. In this study, we developed a hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) drug-repurposing nanoplatform (HA/ZIF-8@BPP/Gem) against pancreatic cancer through the co-delivery of the antitussive benproperine phosphate (BPP) and gemcitabine (Gem). Using cell lines, patient-derived xenograft models, and orthotopic tumor models, we demonstrated that BPP and Gem, rapidly released from the nanoplatform in the acidic tumor microenvironment, exhibited synergistic cytotoxicity without causing significant biochemical abnormalities or organ toxicity. Mechanistically, BPP initiated autophagy but blocked RAB11A-dependent autophagosome-lysosome fusion, thereby converting Gem-induced protective autophagy into a lethal process. In addition, RNA sequencing and flow cytometry analyses revealed that HA/ZIF-8@BPP/Gem stimulated the secretion of immune-related cytokines and activated immune response pathways, particularly T cell-mediated immunity. In conclusion, our study presents a safe and effective strategy of nano-enabled drug repurposing to improve chemotherapy outcomes by inducing amplified autophagy arrest and immune activation in pancreatic cancer.
研究领域:
纳米医学
·
肿瘤学
·
药理学
·
免疫学
·
药物递送
·
癌症治疗
✓ 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）