Materials Today Bio
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2025
·
IF 10.2
Shijia Lu,Chenxiao Zhang,Huiru Wu,Junjie Wang,Jinglong Wang,Limei Zhao,Tianyang Ren,Guofei Li
Liver cancer is one of the malignant tumors with high morbidity and mortality worldwide and lacks effective clinical treatments. CD8 + T cell-based immunotherapy is the most promising option for the treatment of liver cancer, but its application is severely limited by low infiltration and functional exhaustion of CD8 + T cells in liver cancer tissues. To overcome this problem, in this study, pH/matrix metalloproteinase-9 (MMP-9) dual-responsive liposomes were constructed and co-loaded with a galectin-3 (Gal-3) inhibitor, GB1107, a programmed death receptor 1 (PD-1) inhibitor, BMS1166, and an androgen receptor (AR) antagonist, enzalutamide, for immunotherapy studies in liver cancer. Specifically, the co-loaded liposomes (GBE@LP) were produced with a one-two punch targeting antitumor immunity. First, GBE@LP exhibited prolonged circulation in the blood and accumulated in liver cancer tissues through the enhanced permeability and retention effect due to the presence of surface polyethylene glycol. After entering liver cancer tissues, GBE@LP responded to the low pH and overexpression of MMP-9 in the microenvironment to promote the release of GB1107, BMS1166, and enzalutamide, thus, realizing the intelligent release of drugs targeting liver cancer. Upon reaching liver tumor tissues, GB1107 can inhibit overexpressed Gal-3 to transform liver cancer from a “cold” to a “hot” tumor and enable deep penetration by CD8 + T cells. In addition, BMS1166 and enzalutamide inhibit PD-1 and AR in CD8 + T cells, reversing CD8 + T cell exhaustion and enhancing their killing activity. In vivo and in vitro experiments confirmed the significant antitumor effects of GBE@LP in liver cancer. These results indicate that our strategy is expected to reverse the “cold” tumor and immune exhaustion state of liver cancer, which not only improves therapeutic efficacy, but also provides a new paradigm for the exploration of liver cancer immunotherapy.
研究领域:
肿瘤学
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药理学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·Vol. 35
·期 42
·2303718
·
IF 29.4
Shuangquan Gou,Gangyang Wang,Yanan Zou,Wenbo Geng,Tingting He,Zizhen Qin,Lingbin Che,Qian Feng,Kaiyong Cai
Developing a drug delivery platform that possesses universal drug loading capacity to meet various requirements of cancer treatment is a challenging yet interesting task. Herein, a self-assembled gelatin/silk fibroin composite (GSC) particle based drug delivery system is developed via microphase separation followed by desolvation process. Thanks to its preassembled microphase stage, this GSC system is suitable for varying types of drugs. The desolvation process fix drugs inside GSC rapidly and densify the GSC structure, thereby achieving efficient drug loading and providing comprehensive protection for loaded drugs. Actually, the size of this brand-new non-pore dependent drug delivery system can be easily adjusted from 100 nm to 20 µm to fit different scenarios. This work selects GSC with 3 µm diameter as the universal inhaled drug delivery platform, which shows an excellent transmucosal penetration and lung retention ability. Additionally, the MMP-9 sensitive degradation property of GSC enhances the targeted efficiency of drugs and reduces side effects. Intestinally, GSC can self-amplify the regulation of innate immunity to reverse the cancerous microenvironment into an antitumor niche, significantly improving the therapeutic effect of drugs. This study of GSC universal drug platform provides a new direction to develop the next-generation of drug delivery system for lung cancer.
研究领域:
药剂学
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生物材料
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Hao Meng,Jianlong Su,Qi Shen,Wenzhi Hu,Pinxue Li,Kailu Guo,Xi Liu,Kui Ma,Weicheng Zhong,Shengqiu Chen,Liqian Ma,Yaying Hao,Junli Chen,Yufeng Jiang,Linlin Li,Xiaobing Fu,Cuiping Zhang
Chronic diabetic wounds are characterized by prolonged inflammation and excessive accumulation of M1 macrophages, which impede the healing process. Therefore, resolving inflammation promptly and transitioning to the proliferative phase are critical steps for effective diabetic wound healing. Exosomes have emerged as a promising therapeutic strategy. In this study, a smart hydrogel capable of responding to pathological cues in the inflammatory microenvironment to promote the transition from inflammation to proliferation by delivering M2 macrophage-derived exosomes (M2-Exos) is developed. The smart hydrogel is synthesized through the cross–linking of oxidized dextran, a matrix metalloproteinase (MMP)-9-sensitive peptide, and carboxymethyl chitosan containing M2-Exos. In response to elevated MMP-9 concentrations in the inflammatory microenvironment, the hydrogel demonstrates diagnostic logic, adjusting the release kinetics of M2-Exos accordingly. The on-demand release of M2-Exos facilitated macrophage polarization from the M1 to the M2 phenotype, thereby promoting the transition from the inflammatory to the proliferative phase and accelerating diabetic wound healing. The transcriptomic analysis further reveals that the MMP-9-responsive hydrogel with M2-Exos delivery exerts anti-inflammatory and regenerative effects by downregulating inflammation-related pathways. This study introduces an innovative, microenvironment-responsive exosome delivery system that enables precise control of therapeutic agent release, offering a personalized approach for the treatment of chronic diabetic wounds.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yu Zhang,Wu Yang,Wei Xiong,Yu Chen,Pengzhen Zhuang,Haoran Wang,Diana M. Toivola,Yawei Du,Hongbo Zhang,Wenguo Cui
The positive feedback circuit between the complement system and inflammatory immune responses maps the malignant progression of chronic joint inflammation. Prolonged dysregulation of the immune microenvironment in rheumatoid arthritis (RA) further exacerbates sustained complement activation, thereby establishing a vicious cycle. In this study, MMP-9-responsive, injectable micro-nano geneplexes (C5ASO@HAP-CL-TIMP@HMs) are developed for on-demand regulation of complement component C5, aiming to disrupt this pathological circuit. C5 antisense oligonucleotides (C5ASO) are loaded into cationic liposomes, which are subsequently encapsulated within hyaluronic acid microspheres via click chemistry. In vitro, these geneplexes effectively block abnormal C5 activation in RA synoviocytes, restore macrophage polarization balance, reduce pro-inflammatory cytokine levels and immune complex precursor molecules, and upregulate anti-inflammatory mediators. In an adjuvant-induced arthritis rat model, they significantly alleviate joint swelling and cartilage degradation and suppress inflammatory responses, further highlighting the therapeutic potential of geneplexes in dismantling the complement-inflammation circuit. In summary, the development of micro-nano geneplexes capable of precisely disrupting the complement-inflammatory circuit in RA offers a promising new perspective for the targeted treatment of chronic joint inflammation.
研究领域:
免疫学
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纳米医学
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风湿病学
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基因递送
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炎症性疾病
✓ 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）