Nanomedicine
·
2021
·
IF 5.307
Chaoqi Li,Xiangbo Gou,Hui Gao
Aim: The authors aimed to develop Dox@Rg1 nanoparticles with decreased cardiotoxicity to expand their application in cancer. Materials & methods: Dox@Rg1 nanoparticles were developed by encapsulating doxorubicin (Dox) in a self-assembled Rg1. The antitumor effect of the nanoparticles was estimated using 4T1 tumor-bearing mice and the protective effect on the heart was investigated in vitro and in vivo. Results: Different from Dox, the Dox@Rg1 nanoparticles induced increased cytotoxicity to tumor cells, which was decreased in cardiomyocytes by the inhibition of apoptosis. The study in vivo revealed that the Dox@Rg1 nanoparticles presented a perfect tumor-targeting ability and improved antitumor effects. Conclusion: Dox@Rg1 nanoparticles could enhance the antitumor effects and decrease the cardiotoxicity of Dox.Lay abstractDoxorubicin (Dox) is a drug used to treat cancer; however, it can be toxic to the heart. In this study, researchers made nanoparticles containing Dox and a component of ginseng, a root similar to ginger. They tested the nanoparticles in mice with tumors. The nanoparticles appeared to gather at the tumor site in greater amounts than free Dox. In healthy mice, the nanoparticles gathered less in the heart than free Dox. This means that putting Dox into nanoparticles such as these could improve their anticancer effect and decrease harm to the heart.Graphical abstract
研究领域:
药学
·
纳米技术
·
肿瘤学
·
心脏病学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Shuang Yang,Beibei He,Cuiping He,Fengye Zhao,Ran Li,Minfei Shi,Bin Zheng
As a potential drug, antisense oligonucleotides (AO) have considerable application prospects in the field of tumor treatment. However, the main problem to be solved is the lack of an efficient and safe carrier that contributes to reaching the target cancer cells and utilizing the antitumor effect of AO. Here, we designed and developed a novel AO delivery system, which was based on a modified polyethylenimine (PEI) named TPGS-SS-PEI by connecting tocopherol polyethylene glycol succinate (TPGS) to PEI through the disulfide bond (SS) and the biomimetic red blood cell membrane vesicles (RVs). R-TSP/AO was composed of an AO-loaded micelle (TSP/AO) as the “core” prepared by TPGS-SS-PEI, and RVs as the “shell”. The formulations and properties of R-TSP/AO were optimized and characterized. The mean particle size and zeta potential of R-TSP/AO were 109.7 nm and −24.10 mV, respectively. In vitro studies indicated that R-TSP/AO was sensitive to highly reducing conditions and exhibited excellent stability and high security. In addition, R-TSP showed higher AO transfection efficiency and excellent gene silencing efficiency compared with unmodified PEI (P < 0.001). R-TSP/AO exhibited potent tumor inhibition (55.65%) in 4T1 tumor-bearing mice without inducing systemic toxicity. These findings suggested that R-TSP/AO was safe and efficient in enhancing the antitumor efficacy and R-TSP had the potential to be further researched as a carrier for nucleic acid drugs delivery.
研究领域:
药剂学
·
纳米技术
·
分子治疗学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Zhuoya Gao,Jiarong Zhang,Yingchao Hou,Jinjin Lu,Jing Liang,Yufeng Gao,Boqi Li,Shuai Gao,Yanjun Zhao,Min Gao,Jinghua Chen
Both ferroptotic therapy and immunotherapy have been widely employed in cancer treatment. However, ferroptotic cell death fails to induce dendritic cells maturation, which limits the therapeutic outcome of ferroptotic cancer therapy. To address this, the current work reports a tailored liposome to establish a positive loop between ferroptotic therapy and immunotherapy. As the key component of liposome, a unique phospholipid is designed to bear two arachidonic acid tails. The liposome is further surface-engineered with fucose ligand and physically encapsulates immunostimulatory CpG oligodeoxynucleotides (ODNs). The tailored liposome shows enhanced cellular uptake in a model 4T1 cell line. Meanwhile, the high level of reactive oxygen species in cancer cells can induce ferroptosis-specific peroxidation of DAPC and trigger the release CpG ODNs. The CpG ODNs further enable the maturation of dendritic cells and enhance the effector function of CD8 + T cells . IFN-γ released from CD8 + T cells promotes cancer cell ferroptosis via inhibiting SLC7A11 and suppressing the biosynthesis of glutathione . The tailored liposome can also act in synergism with PD-L1 antibody, resulting in enhanced anti-cancer efficacy in a 4T1 tumor-bearing mice model. This work provides a promising strategy for cancer treatment through orchestrating ferroptotic therapy and immunotherapy.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Xin Jin,Qiang Fu,Zehui Gu,Zhenhai Zhang,Huixia Lv
The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA–PEG–PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment . The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Shuting Lu,Wei Feng,Xijuan Yao,Xinran Song,Jinhe Guo,Yu Chen,Zhongqian Hu
Nanodynamic therapy (NDT) based on reactive oxygen species (ROS) generation has been envisioned as a distinct modality for efficient cancer treatment. However, insufficient ROS generation and partial ROS consumption frequently limit the theraputic effect and outcome of NDT owing to the low oxygen (O 2 ) tension and high glutathione (GSH) level in tumor microenvironment (TME). To circumvent these critical issues, we herein proposed and engineered the biodegradable GSH-depletion Mn(III)-riched manganese oxide nanospikes (MnO x NSs) with the photosynthetic bacterial cyanobacteria (Cyan) as a high-efficient and synergistic platform to reshape TME by simultaneously increasing oxygen content and decreasing GSH level. Specifically, under the trigger of acidity, MnO x NSs reacted with photosynthetic oxygen can generate toxic singlet oxygen ( 1 O 2 ). Moreover, MnO x NSs significantly reduced intracellular GSH, resulting in decreased GPX4 activity, which induced tumor cell non-apoptotic ferroptosis . Consequently, this combined strategy based on coadministration with Cyan and MnO x NSs demonstrated the superior antitumor efficacy via amplification of oxidative stress in 4T1 tumor-bearing mice for the synergetic oxygen-augmented nanodynamic/ferroptosis therapy. This work highlights a facile synergistic micro-/nano-system with the specific capability of reshaping TME to augment the sensitivity and therapeutic efficacy of NDT in solid hypoxic tumor therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Xiaoye Yang,Xiaoqun Shi,Jianbo Ji,Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs). The enhanced near-infrared (NIR) fluorescence intensity and reactive oxygen species (ROS) generation of Ce6 were observed in a reductive environment, suggesting the cystamine-switched “ON/OFF” of Ce6. Also, the in vitro release of PTX exhibited a redox-triggered profile. MCF-7 cells showed a dramatically higher uptake of Ce6 delivered by CHT NPs compared with free Ce6. The improved therapeutic effect of PTX/CHT NPs compared with mono-photodynamic or mono-chemotherapy was observed in vitro via MTT and apoptosis assays. Also, the PTX/CHT NPs exhibited a significantly better in anti-tumor efficiency upon NIR irradiation according to the results of in vivo combination therapy conducted on 4T1-tumor-bearing mice. The in vivo NIR fluorescence capacity of CHT NPs was also evaluated in tumor-bearing nude mice, implying that the CHT NPs could enhance the accumulation and retention of Ce6 in tumor foci compared with free Ce6. Interestingly, the anti-metastasis activity of CHT NPs was observed against MCF-7 cells by a wound healing assay, which was comparable to LMWH, suggesting LMWH was promising for construction of nanocarriers for cancer management.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 37
·2204585
·
IF 32.086
Xiu Zhao,Yiyang Wang,Wenxiao Jiang,Qiongwei Wang,Jun Li,Zhiyang Wen,Airong Li,Kaixiang Zhang,Zhenzhong Zhang,Jinjin Shi,Junjie Liu
Virus-based immunotherapy is a promising approach to treat tumor. Closely mimicking the structure and sequential infection processes of natural viruses is highly desirable for effective tumor immunotherapy but remains challenging. Here, inspired by the robust innate immunity induced by herpesvirus, a herpesvirus-mimicking nanoparticle (named Vir-ZM@TD) is engineered for tumor therapy by mimicking the structure and infection processes of herpesvirus. In this biomimetic system, DNAzyme-loaded manganese‑doped zeolitic imidazolate framework‑90 (ZIF-90) nanoparticles (ZM@TD) mimic the virus nucleocapsid containing the genome; the erythrocyte membrane mimics the viral envelope; and two functional peptides, RGD and HA2 peptides, resemble the surface glycoprotein spikes of herpesvirus. Vir-ZM@TD can both effectively evade rapid clearance in the blood circulation and closely mimic the serial infection processes of herpesvirus, including specific tumor targeting, membrane fusion-mediated endosomal escape, and TFAM (transcription factor A, mitochondrial) deficiency-triggered mitochondrial DNA stress, as well as the release of manganese ions (Mn 2+ ) from organelles into the cytosol, ultimately effectively priming cGAS-STING pathway-mediated innate immunity with 68% complete regression of primary tumors and extending by 32 days the median survival time of 4T1-tumor-bearing mice.
研究领域:
生物医学工程
·
癌症免疫疗法
·
纳米技术
·
分子生物学
·
细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Weiya Zeng,Ying Wang,Qing Zhang,Chengyi Hu,Jing Li,Jinwei Feng,Chenglu Hu,Yong Su,Jie Lou,Ling Long,Xing Zhou
Cancer metastasis is the main cause of cancer-related deaths and involves the interaction between tumor cells and neutrophils. In this study, we developed activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys to block neutrophil-mediated cancer metastasis. The aNEM NPs were fabricated by cloaking poly(lactic acid) nanoparticles with membranes derived from activated neutrophils and inherited the functional proteins of activated neutrophils. We demonstrated that aNEM NPs could interfere with the recruitment of neutrophils to the primary tumor and premetastatic niches, inhibit the adhesion of neutrophils to tumor vascular endothelium and circulating tumor cells (CTCs), and disrupt the formation of CTC–neutrophil clusters in vitro and in vivo. In 4T1-bearing mice, aNEM NPs could effectively reduce breast cancer metastasis to various organs in mice. Our results suggest that aNEM NPs are a promising nanomedicine for preventing or treating cancer metastasis by acting as neutrophil nanodecoys.
研究领域:
肿瘤学
·
纳米医学
·
生物医学工程
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2019
·
IF 8.013
Ozioma Udochukwu Akakuru,M. Zubair Iqbal,Chuang Liu,Jie Xing,Zhenni Wei,Zhenqi Jiang,Qianlan Fang,Bo Yuan,Elvis Ikechukwu Nosike,Jianbi Xia,Yinhua Jin,Jianjun Zheng,Aiguo Wu
Magnetic resonance imaging (MRI) signal intensities in tissues are usually enhanced by the injection of metal-based contrast agents (CAs) in patients. Some of these metal compounds have been linked to incurable nephrogenic systemic fibrosis and other neurological disorders, leading to their discontinuation. Herein, we report the design, synthesis, and characterization of a self-assembled metal-free CA which is based on an organic nitroxide radical (4-carboxy-TEMPO) compartmentalized in the biocompatible, biodegradable natural polymer, chitosan (CS), alongside folate targeting for in vivo tumor MRI. This extension conceivably heralds a new application for CS-TEMPO, which hitherto was used in macro-sizes as initiators for grafting CS to various polymers. Significantly, the folic acid (FA)-modified metal-free CA (CS-TEMPO-FA; average size ∼113 nm) is substantially benign, with no evidence of acute toxicity; it exhibits desirable pharmacokinetic profile, enhanced stability in highly reducing environments, high nitroxide loading (molecular relaxivity ∼18.56 mM −1 s −1 ), and effective tumor targeting. This latter characteristic ameliorates the non-specific uptake of CAs by normal cells. CS-TEMPO-FA nanoparticles demonstrate commensurate contrast enhancement of the tumor region up to 1 h post-injection when injected into 4T1 tumor-bearing mice, a contrast enhancement capability hitherto unattained by TEMPO-based CAs. This work points to CS-TEMPO-FA as a potential alternative to metal-based CAs as well as an active folate-targeted metal-free CA for long-term longitudinal tumor MRI which ameliorates the otherwise short in vivo lifetimes of typical organic radicals-based CAs.
研究领域:
生物医学工程
·
纳米技术
·
材料科学
·
医学成像
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Yang Du,Xiaohui Qian,Fenghao Lin,Bingqiang Gao,Weili Wang,Huang Yang,Weilin Wang,Yuan Ding
The therapeutic effects of photothermal therapy (PTT) are dependent on the photothermal conversion efficiency of photothermal agents (PTAs) in tumors and the subsequent activation of the antitumor immune system. However, the insufficient tumor accumulation of current PTAs and the inevitable recruitment of tumor-associated macrophages (TAMs) could further compromise the antitumor activities of PTT. To address these issues, a biomimetic photothermal nanoplatform [email protected] is developed for the targeted remodeling of TAMs, which promotes the antitumor immunity of PTT. Au nanorods with second near-infrared (NIR-II) absorptions are fabricated to serve as PTAs to induce immunogenic cell death in tumor cells. The ferric hydroxide shell coated on Au nanorods can release iron ions to repolarize M2-like TAMs into the tumoricidal M1 phenotype via P38 and STAT1-mediated signaling pathways . Moreover, the surface decoration of platelet membranes endows biomimetic nanoplatform with enhanced tumor targeting ability for precise tumor ablation and TAM regulation. Consequently, [email protected] under NIR-II laser irradiation exhibits significantly higher inhibitory effects in a poor immunogenic 4T1 tumor-bearing mouse model with a 50% complete remission rate compared to conventional PTT (0%). By simultaneously reversing the immunosuppressive tumor microenvironment, this biomimetic nanoplatform offers a promising strategy for enhancing the antitumor efficacy of PTT. Statement of significance The therapeutic effects of current photothermal therapy (PTT) are hindered by the insufficient tumor accumulation of conventional photothermal agents and the recruitment of immunosuppressive tumor-associated macrophages (TAMs) after PTT. Herein, we report a biomimetic iron-based second near-infrared (NIR-II) photothermal nanoplatform ( [email protected] ) for targeted TAMs reprogramming and NIR-II mediated anti-tumor immunity. [email protected] can actively target the tumor site with the help of surface-decorated platelet membranes. Meanwhile, iron ions would be released from [email protected] in acidic lysosomes to reprogram TAMs into tumoricidal M1-like macrophages, which promotes the antitumor responses elicited by NIR-II PTT, thereby contributing to remarkable tumor inhibitory effects, with 50% higher complete remission rate than that of conventional PTT.
研究领域:
纳米技术
·
癌症治疗
·
免疫疗法
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Hui Qiao,Wenxia Zhang,Dongmei Zhang,Wenjun Yan,Jianguo Li,Yingqi Li
The redox homeostasis in tumor cells is an innate defense barrier for reactive oxygen species (ROS)-mediated tumor therapy. Herein, an intratumoral cascade-responsive multifunctional nanodiamond-based platform (NPCD) with a hydrodynamic diameter of 191 ± 5 nm triggering redox dyshomeostasis is fabricated by Cu2+-mediated coordination for polylysinated nanodiamond and doxorubicin (DOX) to achieve cancer-specific diagnosis and therapy. The NPCD nanoplatform enables precise tumor fluorescence localization and chemotherapy through a “turn on” effect due to being specifically activated by GSH to trigger DOX release at a low-pH tumor-specific environment instead of normal cells. Furthermore, NPCD realizes Cu+-based chemodynamic therapy (CDT) and induces GSH depletion by Cu2+ reduction to support CDT. These cause intracellular redox dyshomeostasis, making tumor cells more sensitive to the NPCD nanoparticles. Additionally, NPCD also possesses the intrinsic ability to reverse drug resistance. Of note, NPCD mainly accumulates in the tumor site in 4T1 tumor-bearing mice and enhances the efficacy of therapeutic interventions with negligible side effects. More interestingly, combined with programmed cell death ligand 1 antibody (anti-PD-L1) and imiquimod (R837), NPCD significantly suppresses distant tumor growth, indicating a good immune response. Therefore, this work opens perspectives for the further development of synergistic therapy through a Cu2+-mediated intratumoral cascade reaction.
研究领域:
纳米技术
·
癌症治疗
·
氧化还原生物学
·
药物递送系统
·
免疫肿瘤学
✓ 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）