INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Tao Wu,Jingqiu Zhou,Wanli He,Lei Jin,Tenghui Li,Tianxing Gong,Xu Liu
Chemotherapy is a standard preoperative treatment for locally advanced resectable gastric cancer (GC). However, its efficacy is often limited by the high intracellular glutathione (GSH) levels in tumor cells, which diminish the effectiveness of chemotherapeutic agents. In this study, we developed a GSH-sensitive injectable hydrogel, T-CMC@Fe 3+ (5-FU + GOx), incorporating ferric ions (Fe 3+ ), glucose oxidase (GOx), and 5-fluorouracil (5-FU) for advanced GC multimodal treatment. The hydrogel synergistically enhances anti-tumor activity through multiple mechanisms, including chemodynamic therapy, starvation therapy, and chemotherapy. Thiolated carboxymethyl cellulose (T-CMC) was synthesized by grafting L-cysteine onto carboxymethyl cellulose, with successful preparation confirmed by XPS, FTIR, and 13 C NMR characterizations. The T-CMC@Fe 3+ hydrogel demonstrated responsive degradation of GSH and exhibited favorable biocompatibility in co-culture experiments with GES-1 cells. In vitro analyses revealed that the T-CMC@Fe 3+ (5-FU + GOx) hydrogel significantly enhanced anti-tumor efficacy compared to chemotherapy alone, reducing cell viability to 12.28 ± 2.88 % after 48 h. In vivo studies using cell-derived and patient-derived xenograft models further confirmed its potent anti-tumor effects, with a marked reduction in tumor volume by 14 days (8.12 ± 4.89 mm 3 ). These findings highlight the potential of the T-CMC@Fe 3+ (5-FU + GOx) hydrogel as a novel and effective strategy for enhancing GC treatment through its multimodal therapeutic approach.
研究领域:
药学
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癌症研究
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材料科学
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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
Advanced Science
·
2024
·
IF 14.3
Weiguo Song,Hekai Yang,Ying Wang,Shuzhen Chen,Wenda Zhong,Qian Wang,Wenshuo Ding,Guangzhao Xu,Chen Meng,Ying Liang,Zhe-Sheng Chen,Shuhua Cao,Liuya Wei,Fahui Li
Multi-drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH-sensitive photosensitizer-drug conjugates (CyR-SS-L) are designed and synthesized. CyR-SS-L localized in the mitochondria then is cleaved into CyR-SG and SG-L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR-SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG-L part is used for chemotherapy. CyR-SS-L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR-SS-L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.
研究领域:
肿瘤学
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药学
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生物医学工程
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治疗学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yongyan Deng,Fan Jia,Shengyu Chen,Zhida Shen,Qiao Jin,Guosheng Fu,Jian Ji
A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is developed as an all-rounder for enhanced photodynamic therapy (PDT). By integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest interaction, the nanocarrier could not only deplete intracellular GSH, but also relieve hypoxia at tumor sites through NO mediated blood vessel relaxation. Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity could be produced by the reaction between NO and reactive oxygen species (ROS), generated from α-cyclodextrin (α-CD) conjugated S-nitrosothiol and light-activated chlorin e6 (Ce6) respectively. Due to multiple combined effects between NO and PDT, the NO acts as the loaded gunpowder inside a ‘grenade’, ‘explosively’ amplifying the therapeutic effects that the light responsive ‘fuse’ Ce6 could exert. The present work may well serve as an inspiration for future creative approaches of photodynamic cancer therapy.
研究领域:
癌症治疗
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药学
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纳米技术
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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
Nano Research
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2020
·Vol. 13
·期 1
·160-172
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IF 8.183
Zhang Amin,Zhang Qian,Alfranca Gabriel,Pan Shaojun,Huang Zhicheng,Cheng Jin,Ma Qiang,Song Jie,Pan Yunxiang,Ni Jian,Ma Lijun,Cui Daxiang
Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment. In this regard, we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic. The multifunctional probes consisted of a gold/platinum star-shaped core (Au/Pt star) conjugated with a GSH-sensitive disulfide bond (S–S), a targeting ligand (rHSA-FA), a near-infrared fluorophore (IR780) and glucose oxidase (GO x ). When systemically administered in a xenografted murine model, the probes specifically targeted the tumor sites. As the disulfide linker was cleaved by intracellular GSH, the IR780 molecules could be released for photo-thermal therapy & photodynamic therapy (PTT&PDT) and imaging. Subsequently, the Pt nanolayer of the Au/Pt star and the GO x formed a sequential catalytic system: GO x effectively catalyzed intracellular glucose by consuming oxygen to generate H 2 O 2 and enhance the local acidity, and the Pt layer exhibited peroxidase-like property to catalyze H 2 O 2 producing toxic ·OH for tumor oxidative damage. Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release, real-time imaging ability, and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features, which provides a potential strategy for effective tumor theragnostic.
研究领域:
癌症治疗
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生物化学
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纳米医学
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分子生物学
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产品关联
DOI
高影响因子
BIOMATERIALS
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2022
·
IF 15.304
Yulu Yang,Rui Chen,Yi Gong,Weihu Yang,Ke Li,Wuzhe Fan,Shuangquan Gou,Pengfei Gao,Tingting He,Kaiyong Cai
Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells . Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo . RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment . Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL.
研究领域:
肿瘤学
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血液学
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纳米技术
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免疫治疗
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yun Liu,Ziying Zhang,Yu Xia,Mengnan Ran,Qing Wang,Quanxin Wu,Wenhua Yu,Cao Li,Shiying Li,Ning Guo
In addition to tumor cells, M2-like tumor-associated macrophages (TAMs) also promote tumor progression. Accordingly, the strategy of targeted depletion or repolarization of M2-like TAMs becomes attractive. Here, we report a dual-targeting nanoagent SAMMH to tumor cells and M2-like TAMs for combinatorial tumor treatment. After co-loading the sonosensitizer spafloxacin (SPX) and oxidative phosphorylation inhibitor atavaquone (ATO) into hollow MnO 2 , the addition of Fe 3+ and tannic acid-immobilized hyaluronic acid (HA) caused the formation of SAMMH through generating metal-polyphenol networks (MPNs) coatings outside. In vitro endocytosis assays demonstrated the efficient internalization of SAMMH by both tumor cells and M2-like TAMs through the specific CD44-HA interactions. The GSH-sensitive degradation of SAMMH results in the continuous release of SPX and ATO. Meanwhile, SAMMH could catalyze the endogenous H 2 O 2 to extra O 2 , thus improving the therapeutic effect via the combination of Mn 2+ -induced CDT and O 2 -generation/O 2 -economy dual-enhanced sonodynamic therapy (SDT). Interestingly, SAMMH had a good targeted M2-like TAMs depleting capacity and could promote M2-to-M1 TAMs transformation by CDT-enhanced SDT, leading to a combinational anti-tumor effect. This dual-targeting nanoagent is a promising candidate to achieve CDT-enhanced SDT against both tumor cells and M2-like TAMs, thus providing new insights for the development of highly effective antitumor therapeutics.
研究领域:
癌症治疗
·
纳米医学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 5.9
Kan Li,Shengbin Gui,Ningning Wang,Xiao Li,Chunqin Zhao,Mingyu Liu,Zhen Zhang
Intravenously administered nanoparticles (NPs) often bind with plasma proteins, forming protein corona that prompt rapid systemic clearance, a primary challenge in nanomedicine. In this study, we developed a pH- and GSH-sensitive “stealth” nanodelivery system, PTX@NPs-aPD1-IL, for sequential drug release. By using a biocompatible choline-based ionic liquid (IL) as the coating for NPs, the interaction and adsorption of NPs with serum proteins were reduced, achieving targeted delivery to the lung organ and increasing drug accumulation. In the weakly acidic extracellular tumor microenvironment (pH 6.5), the anti-PD-1 antibody (aPD-1) was first released to block the PD-1/PD-L1 pathway and restore the immunocidal function of T cells. In the highly reductive intracellular environment of tumor cells, the disulfide bonds were cleaved, causing NPs to rupture and release paclitaxel (PTX). It induced tumor cell apoptosis and triggered immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and activated T cells for chemo-immunotherapy. In the mouse orthotopic lung cancer model, PTX@NPs-aPD1-IL exhibited superior efficacy to other treatment groups at the same dose. This was due to the significantly increase in the release of immune factors, including TNF-α and IFN-γ, and the promotion of CD8 + T cells recruitment, which induced a stronger immune response, and thus enhanced the anti-lung cancer effect. In summary, PTX@NPs-aPD1-IL provided a promising strategy for effective chemo-immunotherapy for lung cancer through sequential release profile.
研究领域:
纳米医学
·
肿瘤学
·
药学
·
免疫疗法
✓ 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）