JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yuxin Zhang,Jie Zhou,Xiaoting Chen,Zhiqian Li,Lei Gu,Dayi Pan,Xiuli Zheng,Qianfeng Zhang,Rongjun Chen,Hu Zhang,Qiyong Gong,Zhongwei Gu,Kui Luo
Interaction between carcinoma-associated fibroblasts (CAFs) and tumor cells leads to the invasion and metastasis of breast cancer. Herein, we prepared a redox-responsive chondroitin sulfate (CS)-based nanomedicine , in which hydrophobic cabazitaxel (CTX) was conjugated to the backbone of CS via glutathione (GSH)-sensitive dithiomaleimide (DTM) to form an amphipathic CS-DTM-CTX (CDC) conjugate, and dasatinib (DAS) co-assembled with the CDC conjugate to obtain [email protected] After CD44 receptor-mediated internalization by CAFs, the nanomedicine could reverse CAFs to normal fibroblasts, blocking their crosstalk with tumor cells and reducing synthesis of major tumor extracellular matrix proteins , including collagen and fibronectin . Meanwhile, the nanomedicine internalized by tumor cells could effectively inhibit tumor proliferation and metastasis, leading to shrinkage of the tumor volume and inhibition of lung metastasis in a subcutaneous 4T1 tumor model with low side effects. Collectively, the nanomedicine showed a remarkably synergistic therapy effect against breast cancer by modulating tumor-stromal crosstalk.
研究领域:
肿瘤学
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药学
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纳米技术
·
癌症生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Jiang Tao,Tang Zixiang,Tian Shumiao,Tang Haitian,Jia Zhekun,Li Fangjian,Qiu Chenyue,Deng Lin,Ke Lang,He Pan,Liu Gang,Chu Chengchao,Xiong Yongfu
Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal–organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃] 2 ⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe 3 ⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe 3 ⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered 1 O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe 3 ⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal–ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies. Graphical
研究领域:
纳米医学
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癌症治疗
·
生物无机化学
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生物医学工程
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免疫治疗
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Danrong Hu,Omar Mezghrani,Lei Zhang,Yi Chen,Xue Ke,Tianyuan Ci
Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs.
研究领域:
药学
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纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Rujuan Wang,Haotong Yang,Abdur Rauf Khan,Xiaoye Yang,Jiangkang Xu,Jianbo Ji,Guangxi Zhai
Specific cellular uptake and sufficient drug release in tumor tissues are important for effective cancer therapy. Hyaluronic acid (HA), a skeleton material, could specifically bind to cluster determinant 44 (CD44) receptors highly expressed on the surface of tumor cells to realize active targeting. Cystamine (cys) is sensitive highly reductive environment inside tumor cells and was used as a connecting arm to connect docosahexaenoic acid (DHA) and chlorin e6 (Ce6) to the HA skeleton to obtain redox-sensitive polymer HA-cys-DHA/Ce6 (CHD). Nanoparticles were fabricated and loaded with chemotherapeutic drug docetaxel (DTX) by physical encapsulation. The prepared nanoparticles had significantly increased uptake by MCF-7 cells that overexpressed CD44 receptors, and DTX was effectively released at high reducing condition. Compared with mono-photodynamic therapy (PDT) or mono-chemotherapy, the prepared nanoparticles exhibited superior anti-tumor effect by inhibiting microtubule depolymerization , blocking cell cycle and generating reactive oxygen species (ROS). In vivo anti-tumor experiments proved that DTX/CHD nanoparticles had the best antitumor response versus DTX and CHD nanoparticles under near-infrared (NIR) irradiation. These studies revealed that redox-responsive DTX-loaded CHD nanoparticles held great potential for the treatment of breast cancer.
研究领域:
药学
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纳米技术
·
癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·Vol. 19
·期 40
·2302834
·
IF 13.3
Kaipei Luo,Lu Yang,Chunmei Yan,Yuxin Zhao,Qiuxia Li,Xing Liu,Long Xie,Qiang Sun,Xiaofang Li
Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.
研究领域:
肿瘤学
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药学
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免疫学
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Shaoping Yin,Yi Gao,Yu Zhang,Jianan Xu,Jianping Zhu,Fang Zhou,Xiaochen Gu,Guangji Wang,Juan Li
Deep tumor penetration, long blood circulation, rapid drug release, and sufficient stability are the most concerning dilemmas of nano-drug-delivery systems for efficient chemotherapy. Herein, we develop reduction/oxidation-responsive hierarchical nanoparticles co-encapsulating paclitaxel (PTX) and pH-stimulated hyaluronidase (pSH) to surmount the sequential biological barriers for precise cancer therapy. Poly(ethylene glycol) diamine (PEG-dia) is applied to collaboratively cross-link the shell of nanoparticles self-assembled by a hyaluronic acid–stearic acid conjugate linked via a disulfide bond (HA–SS–SA, HSS) to fabricate the hierarchical nanoparticles (PHSS). The PTX and pSH coloaded hierarchical nanoparticles (PTX/pSH-PHSS) enhance the stability in normal physiological conditions and accelerate drug release at tumorous pH, and highly reductive or oxidative environments. Functionalized with PEG and HA, the hierarchical nanoparticles preferentially prolong the circulation time, accumulate at the tumor site, and enter MDA-MB-231 cells via CD44-mediated endocytosis. Within the acidic tumor micro-environment, pSH would be partially reactivated to decompose the dense tumor extracellular matrix for deep tumor penetration. Interestingly, PTX/pSH-PHSS could be degraded apace by the completely activated pSH within endo/lysosomes and the intracellular redox micro-environment to facilitate drug release to produce the highest tumor inhibition (93.71%) in breast cancer models.
研究领域:
纳米技术
·
癌症治疗
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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
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Jingyi Liang,Yaning Sun,Kaili Wang,Yawen Zhang,Linqing Guo,Zhihong Bao,Dun Wang,Haiyan Xu,Jiani Zheng,Yue Yuan
Chemodynamic therapy (CDT) is an emerging tumor treatment; however, it is hindered by insufficient endogenous hydrogen peroxide (H2O2) and high glutathione (GSH) concentrations in the tumor microenvironment (TME). Furthermore, CDT has limited therapeutic efficacy as a monotherapy. To overcome these limitations, in this study, a nanoplatform is designed and constructed from Cu-doped mesoporous Prussian blue (CMPB)-encapsulated glucose oxidase (GOx) with a coating of hyaluronic acid (HA) modified with a nitric oxide donor (HN). In the proposed GOx@CMPB-HN nanoparticles, the dopant Cu2+ ions are crucial to combining and mutually promoting multiple therapeutic approaches, namely, CDT, photothermal therapy (PTT), and starvation therapy. The dopant Cu2+ ions in CMPB protect against reactive oxygen species to deplete the intracellular GSH in the TME. Additionally, the byproduct Cu+ ions act as a substrate for a Fenton-like reaction that activates CDT. Moreover, H2O2, which is another important substrate, is produced in large quantities through intracellular glucose depletion caused by the nanoparticle-loaded GOx, and the gluconic acid produced in this reaction further enhances the TME acidity and creates a better catalytic environment for CDT. In addition, Cu2+ doping greatly improves the mesoporous Prussian blue (MPB) photothermal conversion performance, and the resultant increase in temperature accelerates CDT catalysis. Finally, the HN coating enables the nanoparticles to actively target CD44 receptors in cancer cells and also enhances vascular permeability. Therefore, this coating has multiple effects, such as facilitating enhanced permeability and retention and deep laser penetration. In vitro and in vivo experiments demonstrate that the proposed GOx@CMPB-HN nanoplatform significantly inhibits tumor growth with the help of in situ enhanced synergistic therapies based on the properties of the TME. The developed nanoplatform has the potential to be applied to cancer treatment and introduces new avenues for tumor treatment research.
研究领域:
纳米技术
·
癌症研究
·
治疗诊断学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Xiaoyu Xu,Zishan Zeng,Jie Chen,Binyao Huang,Zilin Guan,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
Utilizing intratumoral iron mediated Fenton reaction to induce cancer cells destruction, chemodynamic therapy (CDT) is an emerging tumor-specific therapeutic strategy. However, the CDT efficacy is severely restrained by insufficient endogenous H 2 O 2 and catalytic ferrous ions in tumor site. Herein, based on innovative small molecule prodrug design concept, an acid-labile ferrocene-modified cinnamaldehyde prodrug (Fc-CA) was first synthesized. Skillfully combining ROS-generator CA with Fenton catalyst Fc in its molecular structure, Fc-CA could synchronously elevate H 2 O 2 level and catalytic iron amount for enhanced CDT efficacy. Then, hydrophobic Fc-CA was efficiently encapsulated into hydrophilic cyclodextrin-modified hyaluronic acid conjugate (HA-CD) via host-guest interactions, to spontaneously form pH/redox dual-responsive supramolecular catalytic nanoreactor (HA-CD/Fc-CA NPs). The nanoreactor with high drug loading and stability, excellent catalytic activity and tumor specificity could preferentially accumulate in tumor tissues via EPR effect and CD44 receptor-mediated internalization. Through the cleavage of acid-labile hydrazone bond under acidic lysosome environments, the nanoreactor would be dissociated and release pre-protected CA for reinforced oxidation therapy and amplified H 2 O 2 level, which would in turn react with Fc through cascaded Fenton reaction, to generate highly cytotoxic •OH for enhanced cancer killing in a positive feedback process. Both in vitro and in vivo results verified excellent cascade-amplifying therapeutic performance and favorable biocompatibility of this nanoreactor. This study provides an innovative strategy for exploiting versatile organic therapeutic nanoplatforms, simultaneously activating tumor-specific oxidative stress amplification and cascaded enhanced Fenton reaction for superior cancer therapy with excellent biosafety.
研究领域:
纳米技术
·
癌症治疗
·
化学生物学
·
材料科学
·
药学
✓ 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）