COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Xinyu Cui,Minghui Li,Lei Tong,Miaojing Li,Xuefeng Tang,Xiaojun Han
Chemodynamic therapy (CDT) is based on the endogenous generation of cytotoxic hydroxyl free radicals (·OH) with high specificity and selectivity between cancer and normal cells. However, its efficacy is often limited by the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME). Therefore, the combination of CDT with other strategy to realize synergistic therapy is necessary. Herein, a versatile plasmonic Au/Ag nanorods (abbreviated as Au/Ag NRs) via anisotropic Ag overgrowth on Au nanobipyramids was rationally devised to achieve synergistic nanozyme catalytic therapy and near infrared II (NIR-II) light induced photothermal therapy (PTT) with the guidance of computed tomography (CT) imaging. As TME contains high concentrations of H + and H 2 O 2 , Au/Ag NRs exhibited peroxidase (POD) activity to catalyze H 2 O 2 to produce ·OH, inducing cancer cell death. Meanwhile, Au/Ag NRs showed a preeminent NIR-II photothermal effect. More importantly, the enhanced ·OH generation by in-situ heating up resulting from PTT could conversely inhibit the expression of heat shock proteins (HSPs) to abate their resistance to PTT, realizing self-augmented synergistic effect. The NIR-II photothermally enhanced nanozyme catalytic cancer therapy validly inhibited the cancer proliferation, as demonstrated via both cell and animal assays. Moreover, ideal high-contrast CT imaging was realized, owing to the X-ray attenuation capability of elemental Au. The multifunctional Au/Ag NRs hold potential in oncotherapy with imaging capability, high efficiency and low side effects.
研究领域:
癌症治疗
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纳米技术
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光热治疗
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纳米酶
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成像技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Oncology
·
2023
·
IF 5
Jiale Cai,Guiping Hu,Lihua Hu,Junge Chen,Dan Chen,Dan Liu,Xiaolei Wang,Boxian Hu,Cheng Li
Introduction Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. Method In this study, a calcium carbonate (CaCO 3 ) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag 2 S and loaded with l -Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/M L-Arg . Results Non-invasive US-triggered SDT by Ag 2 S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). Conclusion Accordingly, the potential of QD@Ca/M L- Arg- was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.
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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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Jun-Long Liang,Xiao-Kang Jin,Guo-Feng Luo,Shi-Man Zhang,Qian-Xiao Huang,Yan-Tong Lin,Xin-Chen Deng,Jia-Wei Wang,Wei-Hai Chen,Xian-Zheng Zhang
Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, “eat me” signal calreticulin (CRT) was upregulated, while the “don’t eat me” signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.
研究领域:
生物医学工程
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癌症免疫疗法
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药学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yilin Yang,Ning Wang,Zhihua Wang,Mingda Han,Fei Yan,Zhan Shi,Shouhua Feng
Sonodynamic therapy (SDT) has emerged as a promising strategy for treating tumors owing to its non-invasiveness and high tissue-penetrating depth. Improving the efficiency of electron-hole separation of sonosensitizers and alleviation of the hypoxic tumor microenvironment remain major challenges. Metal-organic frameworks (MOFs) have greatly potential in SDT application, however, exploring new sonosensitizers with high reactive oxygen species (ROS) generation and improving the efficacy through a synergistic effect in combination with other therapeutic modalities remain major challenges. Furthermore, the immunosuppressive tumor microenvironment (TME) is characterized by hypoxia, which limit the efficacy of O 2 -dependent cancer treatments including SDT and immunotherapy. Herein, we fabricated a defect-rich titanium-based MOFs using propionic acid-mediated self-templated hierarchical etching. Reductive platinum nanoparticles were embedded onto the surface of MOFs to enhance the spatial separation of electron-hole pairs and improve the quantum yield of ultrasound-generated singlet oxygen ( 1 O 2 ). Finally, perfluorobromooctane was encapsulated in the MOFs to function as an oxygen carrier to develop an oxygen self-feeding nanosensitizer. In vitro and in vivo assays demonstrated that this nanoplatform could produce high levels of 1 O 2 under ultrasound irradiation, which led to enhanced SDT. Moreover, this nanoplatform also relieved the immunosuppressive TME by overcoming hypoxia and enhancing immunogenic cell death to promote the infiltration of tumor-specific cytotoxic T cells into the immunologically “cold” tumor. Therefore, combination of nanoplatform-mediated SDT with anti-PDL1 antibodies effectively inhibited the primary tumors, as well as the metastatic tumors. This study provides an insightful strategy for improving SDT and broadens the application of MOF-based sonosensitizers for sono-immunotherapy.
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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材料科学
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免疫疗法
✓ 已验证
产品关联
DOI
高影响因子
Materials Research Express
·
2024
·
IF 1.8
Wende Fan,Yulin Xie,Yinyuan Zhang,Xiaoju Li,Chunxia Li
Combined chemodynamic/photothermal therapy has great potential in tumor treatment. However, the presence of excessive glutathione (GSH) in the tumor microenvironment (TME) can attenuate its therapeutic effect, and other components in the TME have not been fully utilized as well. In this article, we designed a noble metal nanozyme called PdCu@BSA, which can be used for the combined chemodynamic therapy (CDT) and photothermal therapy (PTT) of tumor. In detail, PdCu@BSA has three different types of enzyme-like activities. Its catalase (CAT)-like activity can degrade extra H2O2 in the TME to create O2 and relieve the hypoxic situation. The glutathione oxidase (GSHox)-like activity can consume high level of GSH in the TME to reduce the consumption of reactive oxygen species (ROS). Peroxidase (POD)-like activity catalyzes H2O2 to form strong oxidized ·OH. The above enzyme-like activities enhance the effectiveness of CDT. Besides, PdCu@BSA has good photothermal effect and can be used for PTT when exposed to 1064 nm laser. Therefore, based on multiple enzyme-like activities and photothermal effects, PdCu@BSA can be employed for synergistic tumor therapy, resulting in good therapeutic outcome.
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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生物化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2021
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IF 9.776
Yudi Deng,Zhijie Jiang,Yincheng Jin,Jianan Qiao,Shan Yang,Hui Xiong,Jing Yao
Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Möbius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of vascular normalization. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to regulate both tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict cytokine functions of angiogenesis and TME deterioration, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4 + and CD8 + T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.
研究领域:
肿瘤学
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纳米技术
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药理学
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免疫学
·
癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
·
IF 11.467
Meirong Huo,Jiyuan Zhou,Honglan Wang,Yuzhao Zheng,Yuqing Tong,Jianping Zhou,Jiyong Liu,Tingjie Yin
Current chemotherapies for metastatic tumors are seriously restricted by limited drug infiltration and deficient disturbance of metastasis-associated complex pathways involving tumor cell autocrine as well as paracrine loops in the microenvironment (TME). Of note, cancer-associated fibroblasts (CAFs) play a predominant role in shaping TME favoring drug resistance and metastasis. Herein, we constructed a tumor extracellular pH (pH e ) sensitive methotrexate-chitosan conjugate (MTX-GC-DEAP) and co-assembled it with quercetin (QUE) to achieve co-delivered nanodrugs (MTX-GC-DEAP/QUE). The pH e sensitive protonation and disassembly enabled MTX-GC-DEAP/QUE for stroma-specific delivery of QUE and positive-charged MTX-GC-DEAP molecular conjugates, thereby achieving deep tumor penetration via the combination of QUE-mediated CAF inactivation and adsorption-mediated transcytosis . On the basis of significantly promoted drug availability, a strengthened “omnidirectional” inhibition of pre-metastatic initiation was generated both in vitro and in vivo from the CAF inactivation-mediated reversion of metastasis-promoting environments as well as the inhibition of epithelial-mesenchymal transition, local and blood vessel invasion via QUE-mediated direct regulation on tumor cells. Our tailor-designed versatile nanodrug provides a deep insight into potentiating multi-faceted penetration of multi-mechanism-based regulating agents for intensive metastasis inhibition .
研究领域:
药学
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肿瘤学
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纳米技术
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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 JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Di Wu,Tiancheng Gong,Zhongxiang Sun,Xihao Yao,Dongzhi Wang,Qiyang Chen,Qingsong Guo,Xiaohong Li,Yibing Guo,Yuhua Lu
The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by deposition of desmoplastic matrix (including collagen and hyaluronic acid). And the interactions between tumor-associated macrophages (TAMs) and tumor cells play a crucial role in progression of PDAC. Hence, the appropriate model of tumor cell-macrophage interaction within the unique PDAC TME is of significantly important. To this end, a 3D tumor niche based on dual-crosslinking gelatin methacrylate and hyaluronic acid methacrylate hydrogels was constructed to simulate the desmoplastic tumor matrix with matching compressive modulus and composition. The bionic 3D tumor niche creates an immunosuppressive microenvironment characterized by the downregulation of M1 markers and upregulation of M2 markers in TAMs. Mechanistically, RNA-seq analysis revealed that the PI3K-AKT signaling pathway might modulate the phenotypic balance and recruitment of macrophages through regulating SELE and VCAM-1. Furthermore, GO and GSEA revealed the biological process of leukocyte migration and the activation of cytokine-associated signaling were involved. Finally, the 3D tumor-macrophage niches with three different ratios were fabricated which displayed increased M2-like polarization and stemness. The utilization of the 3D tumor niche has the potential to provide a more accurate investigation of the interplay between PDAC tumor cells and macrophages within an in vivo setting.
研究领域:
癌症生物学
·
组织工程
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生物材料
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免疫学
·
细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
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2022
·
IF 11.322
Weijuan Zou,Longchen Wang,Junnian Hao,Lixian Jiang,Wenxian Du,Tao Ying,Xiaojun Cai,Haitao Ran,Jianrong Wu,Yuanyi Zheng
Insufficient concentrations of intracellular substrates such as hypoxia and H 2 O 2 considerably reduce the effectiveness of reactive oxygen species (ROS)-associated cancer therapy. Modulating the tumor microenvironment (TME) for augmenting efficacy has become a promising strategy. Herein, a phase-change cascaded nanomedicine (Lap-IrO x @PCM) was constructed via co-encapsulation of iridium oxide nanozyme (IrO x ) and β-lapachone (Lap) by using thermal-responsive phase-change materials (PCMs). After photothermal activation, the protective PCM layer was melted, causing the rapid release of IrO x and Lap. Simultaneously, the peroxidase-like nanozyme IrO x reacted with endogenous H 2 O 2 to liberate highly toxic hydroxyl radicals (•OH) for inducing tumor cell death. Meanwhile, IrO x as another glutathione peroxidase nanozyme also consumed glutathione (GSH) to protect ROS from scavenging. Importantly, the released Lap efficiently generated H 2 O 2 for facilitating the catalytic efficacy of IrO x and provoke the cleavage of heat shock protein 90 (Hsp90) for overcoming tumor heat tolerance in photothermal therapy (PTT). As systematically demonstrated both in vitro and in vivo , this well-defined system achieved a superior antitumor effect via mild photothermal-enhanced nanocatalytic therapy. Our findings have provided the proof of concept of the phase change-mediated, in vivo catalytic activity of nanozymes that can be customized for intensive, TME-mediated, self-enhanced nanocatalytic cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Shiji Fang,Liyun Zheng,Gao-Feng Shu,Chen Xiaoxiao,Xiaoju Guo,Yiming Ding,Wenjing Yang,Jiale Chen,Zhongwei Zhao,Jianfei Tu,Minjiang Chen,Jian-Song Ji
Immunotherapy is the most promising systemic therapy for hepatocellular carcinoma. However, the outcome remains poor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in altering cell-surface protein levels, potentially undermining the efficacy of immunotherapy against tumors. This highlights its potential as a target for antitumor therapy. Herein, CaCO3-based nanoparticles coencapsulated with DOX, an immunogenic cell death (ICD) inducer, and evolocumab was developed to enhanced the efficacy of immunotherapy. The obtained DOX/evolocumab-loaded CaCO3 nanoparticle (named DECP) exhibits a good capacity of acid neutralization and causes ICD of cancer cells. In addition, DECP is able to evaluate the cell-surface level of MHC-I, a biomarker that correlates positively with patients’ overall survival. Upon intravenous injection, DECP accumulates within the tumor site, leading to growth inhibition of hepa1-6 bearing subcutaneous tumors. Specifically, DECP treatment causes augmented ratios of matured dendritic cells, tumor-infiltrating CD8+ T cells and natural killing cells, while concurrently depleting Foxp3+ regulatory T cells. Peritumoral delivery of DECP enhances the immune response of distant tumors and exhibits antitumor effects when combined with intravenous αPD-L1 therapy in a bilateral tumor model. This study presents CaCO3-based nanoparticles with multiple immunomodulatory strategies against hepatocellular carcinoma by targeting PCSK9 inhibition and modulating immune homeostasis in the unfavorable TME.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jinming He,Xijiao Ren,Qiqi Zhang,Shuang Wang,Zhongjun Li,Kaiyong Cai,Menghuan Li,Yan Hu,Qian Ran,Zhong Luo
The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner. The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics.
研究领域:
癌症治疗
·
放射肿瘤学
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免疫疗法
·
纳米技术
·
分子生物学
·
药学
✓ 已验证
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
·
生物医学工程
·
免疫疗法
·
化学生物学
·
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）