Biomaterials Advances
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2025
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IF 6
Mingzhu Zhai,Hongxi Tan,Aohong Xu,Benqing Wu,Fang Xie,Yuanzhi Lu,Yi Zheng
Diabetic foot ulcers (DFU), a severe complication of diabetes mellitus, present a global healthcare challenge due to high risks of limb amputation and mortality. This study developed a multifunctional hydrogel dressing, Gelatin Methacryloyl (GelMA) hydrogel loaded with interleukin-4 (IL-4)-engineered exosomes (Exos), designed to synergistically modulate immune responses and enhance angiogenesis for complete diabetic wound repair. The programmed death-ligand 1 (PD-L1)-enriched Exos were engineered via IL-4 overexpression in NIH3T3 fibroblasts. The GelMA hydrogel loaded NIH3T3 fibroblast-derived Exos with IL-4 overexpression (GelMA/Exos IL-4 hydrogel) exhibited favorable physicochemical characteristics, including a three-dimensional porous microstructure, injectability, tissue adhesion, self-healing properties, and sustained moisture retention. In vitro evaluation demonstrated biocompatibility, sustained exosome release, and enhanced viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In a diabetic wound model, the hydrogel significantly accelerated wound closure, promoted re-epithelialization and angiogenesis, and skewed macrophages toward anti-inflammatory M2 polarization while suppressing T-cell proliferation. These findings highlight the dual immunomodulatory and pro-angiogenic efficacy of GelMA/Exos IL-4 hydrogel, offering a promising therapeutic strategy for chronic wound management.
研究领域:
生物材料学
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再生医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Exploration
·
2025
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IF 22.5
Qi Lu,Hao Ye,Jian Zhao,Xiaoyuan Fan,Kaiyuan Wang,Zeyu Han,Tian Liu,Lili Du,Jiaxuan Song,Helin Wang,Haotian Zhang,Zhonggui He,Jin Sun
The tumor microenvironment is characterized by immunosuppression and compromised intratumoral perfusion, which impairs the effectiveness of immune checkpoint inhibitors and nanomedicines. A significant challenge is the role of activated platelets, as they increase transfer-mediated PD-L1 expression from tumor cells and maintain the integrity of tumor vasculature. These platelets support tumor growth by stabilizing the vasculature and enabling immune evasion, as well as shielding tumor cells from immune detection. To address these platelet-mediated negative antitumor effects, we have developed bioengineered platelets (PTNPs) with surface-anchored ticagrelor-loaded gelatin nanoparticles. This study utilizes the natural tendency of platelets to localize their activated counterparts into tumors. Upon binding to tumor-associated activated platelets, the PTNPs release ticagrelor in response to the secreted matrix metalloproteinases by activated platelet, inhibiting further platelet activation. This reduction in platelet activation lessens platelet-facilitated immunosuppression and diminishes the transferred-PD-L1 expression from cancer cells to platelets, thus enhancing the immune response of anti-PD-L1 therapy. Additionally, this strategy weakens the activated platelets’ contribution to tumor vascular integrity, improving the extravasation and chemotherapeutic efficacy of nanomedicines. Our findings highlight the crucial role of platelet activation in tumor biology and introduce PTNPs as an effective approach to disrupt tumor-supporting platelet activities and enhance anticancer treatments efficacy.
研究领域:
肿瘤生物学
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免疫治疗
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纳米医学
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药理学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
·
2024
·Vol. 67
·期 11
·384-391
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IF 0.9
Shuhua He,Lina Jia,Xiaobei Zheng,Yang Wang,Yuxia Liu,Lan Zhang
Programmed death-ligand 1 (PD-L1) expression is related to the efficacy and prognosis in triple-negative breast cancer. This study employed an indirect labeling method to synthesize [ 125 I]PI-Atezolizumab. The in vitro stability of [ 125 I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [ 125 I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a K d value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD-L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor-bearing mice. A comparison of the biodistribution results between [ 125 I]PI-Atezolizumab and 125 I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [ 125 I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [ 125 I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.
研究领域:
肿瘤学
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分子影像学
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放射性药物
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2022
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IF 15.304
Wenfei Chen,Chunting He,Nan Qiao,Zhaofei Guo,Shilong Hu,Yuanshuai Song,Hairui Wang,Zhirong Zhang,Bowen Ke,Xun Sun
Intratumoral environment as a hypoxic, non-inflamed “cold” state is difficult for many agents to accumulate and activate the immune system. Intrinsically, facultative anaerobic Salmonella VNP20009 target the tumor hypoxic areas, invade into tumor cells and exhibit an immune effect. Here we engineer the bacteria by decorating their surface with newly synthesized heptamethine cyanine dyes NHS–N782 and JQ-1 derivatives to obtain the biohybrid agent N –V-J, leading to the deep tumor targeted photothermal therapy and magnified immunotherapy. Due to the mitochondrial targeting capacity of NHS–N782, N –V-J becomes susceptive to the temperature rise when reaching tumors. This synergistic strategy promotes the systemic immunity by creating an inflamed “hot” tumor state from three different dimensions, which include the inherent immunogenicity of bacteria, the near-infrared laser triggered tumor antigens and the downregulation of PD-L1 expression. All these approaches result in effective and long-lasting T cell immune responses to prevent local and distant tumors for extended time. Leveraging the attenuated bacteria to transport dual drugs to the tumor tissues for self-synthetic vaccines provides a novel paradigm to enhance the bacteria-mediated cancer immunotherapy .
研究领域:
癌症生物学
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免疫学
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治疗学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2022
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IF 18.027
Pei Pei,Yu Zhang,Yunchun Jiang,Wenhao Shen,Hua Chen,Sai Yang,Yanxiang Zhang,Xuan Yi,Kai Yang
Biomaterial-based pleiotropic immune activation may effectively improve the response rate of immunotherapy and enhance the therapeutic effect of the tumor. Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and immune activation of the body. Herein, we construct an inactivated bacteria vector with 125I/131I labeling (125I-VNP/131I-VNP), which could retain radioiodine at the tumor site for a long time and deliver it into tumor cells and a tumor-associated macrophage (TAM), thus achieving efficient internal radioisotope therapy (IRT) of the primary tumor with good biosafety. More importantly, 131I-VNP-mediated local IRT could further stimulate robust systemic antitumor immune responses via activation of the cGAS-STING pathway of innate immunity and promotion of the maturation of DC cells for T-cell-dominated adaptive immunity. After combination with systemic checkpoint blockade therapy (αPD-L1), 131I-VNP, which induces the up-regulation of PD-L1 expression in the distant tumor, could lead to the inhibition of in situ colon cancer and protection against tumor rechallenge. Our strategy pioneers the use of an inactivated bacteria vector as a bridge to cleverly connect radiotherapy and immunotherapy and provide an enlightening idea for radio-immunotherapy mediated by pleiotropic immune activation functions of bacterial vectors.
研究领域:
癌症免疫疗法
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放射生物学
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分子生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
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IF 8.097
Ling Mei,Yayuan Liu,Jingdong Rao,Xian Tang,Man Li,Zhirong Zhang,Qin He
Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were achieved because of the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T cell responses protected mice from tumor recurrence.
研究领域:
肿瘤学
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药学
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免疫学
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纳米技术
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化学
✓ 已验证
DOI
PubMed
高影响因子
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