MACROMOLECULAR BIOSCIENCE
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2024
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IF 4.4
Anqi Xu,Yuchen Sun,Mingyu Guo
Polyaspartic acid derivatives are a well-known kind of polypeptide with good biocompatibility and biodegradability, and thus have been widely used as biomedical materials, including drug-loaded nano-scale micelles or macroscopic hydrogels. In this work, for the first time, monodisperse polyaspartic acid derivative microspheres with diameter ranging from 120 to 350 µm for potential tumor embolization therapy are successfully prepared by single emulsion droplet microfluidic technique. The obtained microsphere shows fast cationic anticancer drug doxorubicin hydrochloride loading kinetics with high loading capacity, which is much better than those of the commercial ones. Additionally, drug release behaviors of the drug-loaded microspheres with different diameters in different media are also studied and discussed in detail. These results provide some new insights for the preparation and potential application of polyaspartic acid derivative-based monodisperse microspheres, especially for their potential application as embolic agent.
研究领域:
生物医学工程
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药学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
·
2025
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IF 8.7
Qi Zhang,Yezhen Tan,Qiyang Liang,Liangyou Gu,Yue Shi,Yan Huang,Xiubin Li,Jie Qi,Cheng Peng,Hanfeng Wang,Yaohui Wang,Kan Liu,Tianwei Cai,Yudan He,Qingbo Huang,Xu Zhang,Baojun Wang,Xin Ma,Weimin Ci
Preoperative downstaging of renal cell carcinoma with a tumor thrombus (RCC-TT) makes thrombectomy feasible. However, treatment resistance is common and may partly be attributed to the tumor-promoting role of the tumor microenvironment (TME). Herein, we sequenced, integrated, and comprehensively analyzed multi-center, multi-omics data from 164 RCC-TT patients and identified two clinically relevant RCC-TT subtypes. We find that the poor-prognosis subtype (TT1) exhibits enhanced extracellular-matrix (ECM) remodeling driven by epithelial LOX expression. Spatial transcriptomics (ST) shows the co-localization of GPNMB + macrophages, THBS2 + fibroblasts, and LOX + malignant cells around tumor nests in TT1 tumors, reinforcing tumor immune barriers (TIBs). Our extensive validations using cell lines, syngeneic mouse models, multiplex immunofluorescence staining, and large-scale RCC cohorts underscore the potential of LOX inhibition in disrupting TIBs, sensitizing RCC to immunotherapy, and overcoming treatment-induced phenotypic plasticity. This study provides insights into the biological underpinnings and prognosis assessment of RCC-TT, demonstrating targetable ECM-remodeling vulnerabilities.
研究领域:
肿瘤学
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分子生物学
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免疫学
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生物信息学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Yanqiao Ren,Yusheng Guo,Bo Sun,Licheng Zhu,Wenlong Wu,Bin Liang,Xiangjun Dong,Chuansheng Zheng
Transarterial chemoembolization (TACE) requires the complete embolization of tumor vessels. However, after embolization, tumor hypoxia and angiogenesis increase, and copper ions (Cu 2+ ) play a key role in the regulation of angiogenesis. Decreasing the undesirable release of Cu 2+ into serum and tumor tissues is a major challenge in the use of TACE. In this study, we constructed an adhesive injectable thermosensitive hydrogel (poly(N-isopropylacrylamide-codopamine methacrylamide), PND) loaded with a small Cu chelator (SO-N) for use in synergistic tumor embolization; this agent is called PNDS. SO-N chelates Cu 2+ in a highly selective manner and can effectively consume the biocopper that is involved in angiogenesis. In addition, the adhesive thermosensitive hydrogel rapidly formed a gel in situ , which further inhibited the local blood ny to the tumor and accelerated ischemic necrosis. Moreover, the ability of PNDS to efficiently chelate Cu 2+ and inhibit angiogenesis was investigated in vitro . Our in vivo experiments demonstrated that PNDS can promote tumor necrosis, reduce tumor Cu 2+ levels, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This study is the first to show elevated serum Cu 2+ levels in liver cancer patients with TACE failure/refractoriness; PNDS provides a promising approach for improving the efficacy of TACE for liver cancer by regulating Cu homeostasis.
研究领域:
肿瘤学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
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