INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Wenhui Liu,Ruyu Cao,Yongye Shen,Yaxin Lu,Shuqi Li,Shen Li,Guochen Su,Jing Xu,Yuanqiang Guo
A self-assembling nanoplatform based on FOB (a heteropolysaccharide from Fomitopsis officinalis ) named QU@FOB-FcDBA was developed in this study. A dynamic boronate ester bond, a pH-sensitive covalent linkage formed through reversible dehydration reactions, linked FOB and 1,1′-ferrocenediboronic acid (FcDBA) while encapsulating the hydrophobic drug quercetin (QU). The formulation not only enhanced the water solubility of QU, but also indirectly improved the clinical utilization rate of QU. QU@FOB-FcDBA exhibited unique dual pH/ROS-responsive characteristics, enabling precise recognition and selective response to the acidic microenvironment and elevated reactive oxygen species (ROS) levels in tumor tissues. This ensured the accurate and controlled release of QU and FcDBA, achieving synergistic deep penetration and enhanced therapeutic efficacy through the combined induction of ferroptosis and chemotherapy. In vivo , QU@FOB-FcDBA effectively suppressed tumor progression and metastasis. Mechanistically, it induced cell death via multiple pathways: triggering ferroptosis through ROS accumulation, lipid peroxidation (LPO), and glutathione (GSH) depletion, as well as inducing apoptosis. In vitro , FOB upregulated macrophage surface markers (CD40, CD80, CD86, MHC-II) and nitric oxide (NO) expression. This innate immune activation may directly contribute to antitumor effects and establish a favorable immune microenvironment for immunotherapy. These results position QU@FOB-FcDBA as a promising platform integrating ferroptosis induction and chemotherapy for improved cancer treatment.
研究领域:
纳米医学
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癌症治疗
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药物递送
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生物化学
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免疫学
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药理学
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材料科学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Rui Ni,Lele Huang,Zhen Li,Wenli Zhang,Yajie Wang,Yan Shen,Jianxin Wang,Weigen Lu
Purpose To enhance tumor penetration by formulation design and tumor microenvironment (TME) modulation, herein a novel reactive oxygen species (ROS)-responsive size/shape transformable lipid-polymer hybrid nanoparticle (LPN) has been fabricated for the co-delivery of an anticancer and collagen-inhibition drug. Methods A ROS-responsive poly(D, L-lactide)-thioketal-polyethylene glycol (PLA-TK-PEG) co-polymer was synthesized. LPNs were then fabricated by encapsulation of losartan (LST)-loaded micelles as the core to support paclitaxel (PTX)-loaded liposomes. The PEG content in the lipid shell of LPNs was then adjusted to obtain the size-/shape-transformable LPNs (M/LST-Lip/PTX-PEG 5% ). The ROS-responsiveness was observed in vitro by transmission electron microscopy and the tumor-penetration of the LPNs was evaluated in 3D tumor spheroids by confocal laser scanning microscopy. Tumor-targeting, tumor-penetrating, and antitumor efficacies of the NPs in 4T1 tumor-bearing mice were determined by in vivo imaging. Results ROS-responsive micellar core degradation and the transformation of spherical LPNs (120nm) to smaller 40 mm discoid nanoparticles (NP) were observed. The transformable LPNs exhibited enhanced capacity of penetration in contrast to the un-transformable preparations in three-dimensional (3D) tumor spheroids. Furthermore, synergetic penetrating enhancement was achieved by LST-loaded transformable LPNs in 4T1 and fibroblast cell mixed 3D tumor spheroids. The improved tumor penetration of LST-loaded transformable LPNs was observed in vivo, which could be due to their collagen inhibiting and size/shape transformable effect. Due to their enhanced penetrability, LST and PTX-loaded transformable LPNs demonstrated significant in vivo antitumor efficacy in comparison to other preparations. Conclusion The results confirmed the efficacy of M/LST-Lip/PTX-PEG 5% in tumor targeting, collagen inhibition in TME, and enhanced tumor penetration. This novel drug delivery system can therefore play a substantial role in improving the therapeutic efficacy of antitumor drugs combined with TME-improving agents.
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
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Wensheng Xie,Jielin Ye,Zhenhu Guo,Jingsong Lu,Wanling Xu,Xiaohan Gao,Hongye Huang,Renjian Hu,Liucheng Mao,Yen Wei,Lingyun Zhao
Mitochondrial calcium ions (Ca 2+ ) overload, an abnormal accumulation of free Ca 2+ in mitochondrial, has become a potential strategy for effective cancer treatment. Inspired by mitochondrial Ca 2+ overload-induced ROS generation, a tumor microenvironment (TME)-responded full-degradable [email protected] 2 O-TPP NCs are successfully fabricated for effective chemodynamic therapy (CDT) via toxic hydroxyl radical ( ∙ O H ) bursting. The as-synthesized nanocatalysts are stable and safe in normal tissues but will quickly degrade into Ca 2+ and cuprous ions (Cu + ) under the acidic TME. The mitochondrial Ca 2+ overload effectively simulates extra H 2 O 2 generation. Then Cu + catalyzes the produced H 2 O 2 into toxic ∙ O H to kill the tumor cells via Fenton-like reaction. Meanwhile, abundant GSH in tumor cells can further reduce Cu 2+ into Cu + to enhance the CDT effect. Both in vitro and in vivo evaluations demonstrate the efficient anti-tumor effect of [email protected] 2 O-TPP NCs via mitochondrial Ca 2+ overload-induced ∙ O H bursting. We believe that the development of [email protected] 2 O-TPP NCs will be an amazing inspiration for designing safe and green chemodynamic nanocatalysts for highly efficient cancer treatment.
研究领域:
肿瘤学
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纳米技术
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化学工程
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生物医学工程
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产品关联
DOI
高影响因子
BIOCONJUGATE CHEMISTRY
·
2024
·
IF 4
Ruiqi Sun,Yuxin Wang,Wenhui Shi,Hongfu Zhang,Jianhua Liu,Weina He
Cancer which causes high mortality globally threatens public health seriously. There is an urgent need to develop tumor-specific near-infrared (NIR) imaging agents to achieve precise diagnosis and guide effective treatment. In recent years, imaging probes that respond to acidic environments such as endosomes, lysosomes, or acidic tumor microenvironments (TMEs) are being developed. However, because of their nonspecific internalization by both normal and tumor cells, resulting in a poor signal-to-noise ratio in diagnosis, these pH-sensitive probes fail to be applied to in vivo tumor imaging. To address this issue, a cholecystokinin-2 receptor (CCK2R)-targeted TME-sensitive NIR fluorescent probe R2SM was synthesized by coupling pH-sensitive heptamethine cyanine with a CCK2R ligand, minigastrin analogue 11 (MG11) for in vivo imaging, in which MG11 would target overexpressed CCK2Rs in gastrointestinal stromal tumors (GISTs). Cell uptake assay demonstrated that R2SM exhibited a high affinity for CCK2R, leading to receptor-mediated internalization and making probes finally accumulated in the lysosomes of tumor cells, which suggested in the tumor tissues, the probes were distributed in the extracellular acidic TME and intracellular lysosomes. With a pKa of 6.83, R2SM can be activated at the acidic TME (pH = 6.5–6.8) and lysosomes (pH = 4.5–5.0), exhibiting an apparent pH-dependent behavior and generating more intense fluorescence in these acidic environments. In vivo imaging showed that coupling of MG11 with a pH-sensitive NIR probe facilitated the accumulation of probe and enhanced the fluorescence in CCK2R-overexpressed HT-29 tumor cells. A high signal was observed in the tumor region within 0.5 h postinjection, indicating its potential application in intraoperative imaging. Fluorescence imaging of R2SM exhibited higher tumor-to-liver and tumor-to-kidney ratios (2.1:1 and 2.3:1, respectively), compared separately with the probes that are lipophilic, pH-insensitive, or MG11-free. In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.
研究领域:
医学成像
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癌症生物学
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 39
·16571-16588
·
IF 7.79
Yu Zhang,Yifeng Yang,Jinsheng Shi,Lili Wang
Weak acidity (6.5–6.9) and limited H2O2 level in the tumor microenvironment (TME) usually impact the therapeutic effect of chemodynamic therapy (CDT) for cancer. A Specific TME promotes the formation of an immunosuppressive microenvironment and results in high rate of recurrence and metastasis of cancer. Fe3O4@ZIF-8/GOx@MnO2 multi-layer core shell nanostructure was constructed as a hybrid nanozyme. After magnetic targeting of the tumor site, the outermost MnO2 shell catalyzed H2O2 in TME to produce O2 and was broken due to the reaction with glutathione. Due to the acid response, the ZIF-8 layer would crack and release glucose oxidase (GOx) and Fe3O4. The generated O2 was utilized by GOx in starvation therapy to consume glucose and produce H2O2 and gluconic acid. The Fenton reaction efficiency of Fe(II) was improved by the increased H2O2 concentration and the enhanced acidity in TME. At the same time, the intrinsic photothermal effect of Fe3O4 upon 808 nm laser irradiation promoted the activity of MnO2 and GOx as oxidase, and Fe(II) as catalase-like, and ablated the primary tumor. Moreover, the hybrid nanozyme can facilitate the transformation of M2-type macrophages to M1-type, and strong systemic antitumor immune effect was induced. A synergy of multiple therapeutic modes including starvation therapy, CDT, photothermal therapy (PTT), and immunotherapy can be realized in the hybrid nanozyme for tumor therapy.
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
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Jing Yan,Qinghua Wu,Ziyin Zhao,Jianhua Wu,Huan Ye,Qiujun Liang,Zhuchao Zhou,Mengying Hou,Xudong Li,Yong Liu,Lichen Yin
The anticancer performance of nanomedicine is largely impeded by insufficient intratumoral penetration. Herein, tumor microenvironment (TME)-amendatory and self-adaptive nanoclusters (NCs) capable of cancer-associated fibroblasts (CAFs) depletion and size/charge conversion were engineered to mediate light-assisted, hierarchical intratumoral penetration. Particularly, large-sized NCs (~50 nm) were prepared via self-assembly of FAP-α-targeting peptide-modified, 1 O 2 -sensitive polymers, which were further used to envelope small-sized dendrimer (~5 nm) conjugated with Ce6 and loaded with DOX (DC/D). After systemic administration, the NCs efficiently targeted CAFs and generated lethal levels of 1 O 2 upon light irradiation, which depleted CAFs and concomitantly dissociated the NCs to liberate small-sized, positively charged DC/D. Such stroma attenuation and NCs transformation collectively facilitated the delivery of DC/D into deeper regions of CAF-rich tumors, where DOX and 1 O 2 provoked synergistic anti-cancer efficacies. This study provides an effective approach to facilitate the tumor penetration of nanomedicine by concurrently and spatiotemporally reconfiguring the nano-properties and remodeling the TME.
研究领域:
纳米技术
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癌症治疗
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药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
·
2022
·
IF 6.76
Mengchao Ding,Xiaoying Kong,Weiyan Chen,Lei Yan,He Huang,Zunzhou Lv,Peng Jiang,Ali Mu,Congcong Huang,Jinsheng Shi
Single cancer starvation therapy (ST) strategy can’t achieve satisfactory anti-tumor effect, mainly due to the diversified nutritional sources of tumor cells. Herein, [email protected] 2 @2-Deoxy-D-glucose(2-DG)-CaCO 3 -RGD nanoparticles (CADCR NPs) were prepared for three-pathway blocking for efficient starvation therapy as well as reinforced photothermal therapy (PTT) and chemodynamic therapy (CDT). After CADCR NPs were targeted to tumor cells, CaCO 3 was ruptured in the acidic environment, releasing Ca 2+ to chelate glutamine and cutting off the glutamine metabolic pathway of the tumor. 2-DG was also released from mesoporous SiO 2 and restrained the glycolytic pathway of tumor cells. In addition, under the thermal stimulus of near-infrared irradiation, axitinib was released from CuS NPs, which inhibited the proliferation of tumor blood vessels, ultimately inhibiting the aerobic respiratory pathway of tumor cells. Interestingly, CADCR NPs also showed potential to reshape the tumor microenvironment (TME) and promoted the transformation of macrophages from M2 to M1 type, increasing the expression of CD8+ T cells in the tumor site. In conclusion, CADCR NPs achieve severe tumor starvation by simultaneously interfering with three energy metabolic pathways, and further enhance tumor treatment with the aid of PTT, CDT, and TME improvement, which exhibits great potential for clinical cancer therapy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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肿瘤微环境
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细胞代谢
✓ 已验证
产品关联
DOI
高影响因子
TRANSFUSION MEDICINE
·
2021
·Vol. 31
·期 4
·277-285
·
IF 2.019
Hongtian Chen,Piao Lv,Ziwei Liu,Wanjun Chen,Yuan Yao,Chixiang Liu,Qiong Cao,Huayou Zhou
Objectives The purpose of this study was to investigate the association and impact of TMEM50A on RH genes activity and function. Background SMP1 is located on chromosome 1p36.11 in the RH gene locus, between the RHD and RHCE gene, where its position may be linked to RH haplotypes and contribute to selective pressures regarding certain RH haplotypes. TMEM50A is encoded by the SMP1 located in the intergenic region of RH , its influence on the function of the RH genes remains unclear. Methods The expression of TMEM50A was regulated by transfection of plasmid and siRNA in K562 cell model. Western blot and real-time PCR were used to detect possible expression changes in the RH . The ammonium transport function of cells was monitored using pH-sensitive dye, while transcriptome sequencing was used to predict the potential function of TMEM50A. Results The overexpression of TMEM50A significantly up-regulated RHCE gene activity (63.56%). The inhibition of TMEM50A resulted in significantly decreased RHCE (41.82%) and RHD expression (27.35%). Compared to control group, there was no significant change in the NH 4 + transport function of cells in the overexpressed TMEM50A group. Transcriptome analysis showed that TMEM50A not only affected the transcription of target gene through splicing activities, but also played a role in the development of embryonic nervous system. Conclusions TMEM50A may regulate the expression of RH gene by affecting the stability of RH mRNA through splicing function. It speculates that TMEM50A may play an important role in the development of embryonic nervous system.
研究领域:
分子生物学
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遗传学
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细胞生物学
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转录组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2025
·
IF 10.9
Xueting Liu,Dingze Zhou,Yuxi Zhang,Zonghui Zhao,Wenhao Zhao,Xia Wang,Qigang Wang
Tumor cells, due to their reliance on aerobic glycolysis, contribute to the tumor microenvironment (TME), which is characterized by lactate accumulation and redox imbalances. Targeting lactate, a key metabolic substrate in the TME, a novel strategy combining gene therapy with enzyme dynamic therapy (EDT) has been proposed. This strategy utilizes a cascade oxidase-peroxidase system, which induces tumor DNA damage while simultaneously inhibiting repair mechanisms. By mimicking the construction of multienzyme complexes, a highly active and well-ordered oxidase-peroxidase and gene platform (ASO-miR21/DLC-NGs) has been developed. The platform is based on dextran-confined lactate oxidase (LOx) and chloroperoxidase (CPO) pairs, followed by small molecule monomer-induced diffusion-controlled self-terminating polymerization for efficient loading of Antisense Oligonucleotide targeting microRNA-21 (ASO-miR21). By precisely regulating the dimensions (nanoscale to microscale) and crosslinking density, this approach overcomes the limitations of traditional multi-enzyme systems, such as poor stability and inefficient substrate diffusion. The synergistic effects of DNA damage and anti-repair are achieved by catalytically regulating reactive oxygen species (ROS), which reverses the redox balance and downregulates miR21 expression, inhibiting tumor cell proliferation. The catalytic transformation research of metabolic substrates of abnormal tumor microenvironment and the multi-pathway design with the metabolic regulation can provide important insights for specialized or interdisciplinary researchers on the multipathway cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-14
·
IF 3.8
Liu Qiang,Xiang Yurong,Yu Qiang,Lv Quan,Xiang Zheng
Colorectal cancer cells are highly heterogeneous and exhibit various drug resistances, making personalized treatment necessary. This typically involves a combination of different treatment modalities such as surgery, radiation, and chemotherapy to increase patient survival. Inspired by this, synergistic therapy, which combines multiple modalities into a single nanotherapeutic drug, shows promise in treating cancer. In this study, a nano-catalyst based on calcium peroxide (CaO 2 ) and the chemotherapeutic drug doxorubicin hydrochloride (DOX) co-loaded into HPB nanoparticles (HPB@CaO 2 /DOX-PAA) was developed to achieve synergistic cancer treatment through chemodynamic/chemo/photothermal (CDT/CT/PTT) mechanisms. After being endocytosed by cancer cells, the nano-catalyst decomposes, releasing cargo. During near-infrared light irradiation, HPB induces a photothermal effect, DOX exhibits significant RNA and DNA destruction capabilities, meanwhile CaO 2 produces a large amount of H 2 O 2 in the moderately acidic TME, which combines with Fe 2+ ions derived from HPB to form the highly toxic •OH in a Fenton-like reaction, enhancing the chemodynamic treatment. Assays conducted ex vivo and in vivo have exhibited the efficacy of this triple synergistic therapeutic regimen, indicating its potential clinical application.
研究领域:
肿瘤学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2022
·Vol. 46
·期 15
·6932-6939
·
IF 3.925
Gang Chen,Yu Wang,Xueping Kong,Hongwei Li,Bao Li,Xianghui Yu,Lixin Wu,Yuqing Wu
The intrinsic features of tumors often give rise to unsatisfactory outcomes of photothermal treatment (PTT). Remarkably, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H2O2), and low pH has proven to be a tremendous obstacle for tumor treatment. Therefore, developing an effective photosensitizer that can respond to both NIR radiation and TME is imperative but remains a challenge. Here, we explore a molybdenum-based polyoxometalate (Na15[MoVI126-MoV28O462H14(H2O)70]·400H2O, [Mo154]) as a photosensitizer for TME-manipulated PTT enhancement because of the following features. Firstly, the 808 nm absorption of [Mo154] can be increased via pH-induced aggregation; secondly, due to the unique multi-electron property, [Mo154] can deplete cysteine and reactive oxygen species (ROS) via redox reactions; thirdly, reduced [Mo154] ([rMo154]) can further improve the 808 nm absorption by promoting the transition from Mo(VI) to Mo(V). Consequently, [Mo154] can overcome several obstacles in TME and thus improve the PTT efficiency by synergizing the effects of pH-induced aggregation, cysteine reduction and depletion, and free-radical scavenging. In addition to providing a promising photosensitizer for PTT, this finding extends the application of molybdenum-based polyoxometalates in the biomedical field.
研究领域:
癌症治疗
·
生物医学工程
·
材料科学
·
光化学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2026
·
IF 14.1
Kepeng Hu,Jiawei Wang,Wei Zhang,Zhixuan Wu,Jing Chen,Yujing He,Xiyue Duan,Yaoting He,Xin Xin,Haoyi Xiang,Yijing Wang,Chengwei Wu,Yang Yi,Qing Meng,Yuqian Qiao,Kui Cheng,Xiaojun Long,Zhangfa Song
The precise activation of the cGAS-STING pathway for effective tumor immunotherapy remains a significant challenge due to the complexity of immune responses and tumor microenvironment (TME) limitations. Here, a multifunctional nanoagonist, cRGD-PDA/ZIF8@ICG/TPT (cDZ@IP), was developed to realize nano-metabolite–driven multimodal synergistic activation of the STING pathway and enhanced immune recognition. The agonist combines cRGD peptide-targeted polydopamine-coated zeolitic imidazolate framework-8 with the photosensitizer indocyanine green and the chemotherapeutic drug topotecan. Upon near-infrared laser irradiation, cDZ@IP degrades within the TME, generating high levels of reactive oxygen species, inducing mitochondrial stress, and releasing endogenous mitochondrial DNA. Additionally, topotecan enhances DNA damage accumulation by inhibiting nuclear DNA repair. Zn 2 + released from the agonist further amplifies cGAS-STING pathway activation, thereby ensuring a robust immune response. The mild photothermal therapy-induced immunogenic cell death promotes the initiation of antitumor immunity, while also enhancing the effectiveness of immune checkpoint blockade. In vivo studies show that cDZ@IP significantly inhibits primary and distant tumor growth and prevents lung metastasis, providing a promising strategy for STING pathway-targeted cancer immunotherapy.
✓ 已验证
DOI
PubMed
高影响因子
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