GYNECOLOGIC ONCOLOGY
·
2025
·
IF 4.1
Hanfei Xie,Lu Sun,Shili Yao,Xuefei Tian,Liming Jin,Yujie Dai,Yuanzheng Li,Yuxuan Li,Jianmin Fang,Peng Guo,Yingli Zhang
Objective The incidence of mortality and morbidity from endometrial cancer (EC) is increasing annually, and there is a paucity of effective targeted therapies for the condition. Antibody-drug conjugates (ADCs) represent a promising approach to tumor-targeted therapy. In this study, we aim to identify a novel molecular target for the preclinical development of EC-targeted ADCs. Methods Through quantitative and unbiased bioinformatics analyses intercellular adhesion molecule-1 (ICAM1) was identified as a potential cell membrane target. Two ADCs, ICAM1-MMAE and ICAM1-DXd, were subsequently developed by conjugating ICAM1 monoclonal antibodies with microtubule inhibitors and DNA topoisomerase inhibitors, respectively. The preclinical efficacy and biosafety of these ICAM1 ADCs were validated in both in vitro and in vivo models. Furthermore, transcriptomic analysis was conducted to elucidate the therapeutic effects of the ICAM1 ADCs. Results Quantitative flow screening and bioinformatics analyses revealed significant overexpression of ICAM1 in EC. ICAM1-MMAE and ICAM1-DXd were developed using clinically effective linkers and payloads. In preclinical models, ICAM1 ADCs showed superior antitumor efficacy compared to standard chemotherapy, achieving sustained tumor regression with an excellent safety profile in both subcutaneous and orthotopic xenograft models. Transcriptomic analysis further revealed that ICAM1-DXd potently activated tumor immunity. Conclusions ICAM1 was identified as a promising cell membrane protein target for ADC development in EC. As-synthesized ICAM1 ADCs demonstrated potent antitumor activity, favorable biosafety profiles in vitro and in vivo , and the ability to activate tumor immunity. These findings support the potential of ICAM1 ADCs as a therapeutic strategy and warrant further investigation in clinical studies.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Hao Wu,Changcheng Chen,Jiangfeng Li,Dongmei Yu,Xun Wu,Hai Huang,Zhen Tang,Qi Wu,Shichao Yan,Ning Wang,Mo Wang,Feilong Wei,Yunlong Yu,Duan Wang,Mengting Shi,Xusong Yue,Pengfei Cao,Zenghui Zheng,Xiaokang Li,Baolin Guo,Lei Shi,Zheng Guo
Infectious bone defects pose significant clinical challenges due to persistent infection and impaired bone healing. Icam1+ macrophages were identified as crucial and previously unrecognized regulators in the repair of bone defects, where impaired oxidative phosphorylation within this macrophage subset represents a significant barrier to effective bone regeneration. To address this challenge, dual-responsive iron-doped barium titanate (BFTO) nanoparticles were synthesized with magnetic and ultrasonic properties. These nanoparticles were further loaded with the anti-inflammatory agent curcumin and coated with engineered mesenchymal stem cell membranes (EMM) modified with γ3 peptide, creating BFTO-Cur@EMM nanoparticles specifically designed to target Icam1+ macrophages. These nanoparticles were shown to disrupt bacterial biofilms under alternating magnetic fields (AMF) and to activate oxidative phosphorylation and osteogenic immune responses in Icam1+ macrophages via low-intensity pulsed ultrasound (LIPUS). Transcriptomic sequencing and validation experiments demonstrated that this approach activates oxidative phosphorylation (OXPHOS) by stimulating the JAK2-STAT3 pathway and inhibiting the MAPK-JNK pathway, thereby promoting the polarization of Icam1+ macrophages toward a pro-reparative phenotype and enhancing the secretion of pro-angiogenic and osteogenic cytokines. These nanoparticles were subsequently integrated into quaternized chitosan (QCS) and tricalcium phosphate (TCP) to create a bioink for three-dimensional (3D) printing anti-infection QT/BFTO-Cur@EMM bone repair scaffolds. In vivo studies indicated that these scaffolds significantly improved the healing of infectious bone defects without causing thermal damage to surrounding tissues. This work highlights the potential of this material and the targeting of Icam1+ macrophages as an effective strategy for simultaneously controlling infection and promoting bone regeneration.
研究领域:
生物材料
·
纳米技术
·
骨科
·
免疫学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
·
2021
·
IF 3.786
Qian Gong,Xiuming Zhang,Aifeng Liang,Sinian Huang,Guangang Tian,Mengjiao Yuan,Qing Ke,Yijun Cai,Bin Yan,Jin Wang,Jinjin Wang
Background and aims Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. Methods This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. Results The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues( P < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. Conclusion The ICAM1 and APMAP may serve as a potential tumor marker for CRC.
研究领域:
肿瘤学
·
蛋白质组学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2026
·
IF 4.3
Mifang Yang,Jingjing Wu,Yuan Jing,Siyu Chen,Rongrong Cao,Heming Wu,Hongming Du,Zhirui Guo,Fan Zhang,Wei Shu,Yi Yuan
Oral squamous cell carcinoma (OSCC), the most common oral malignancy, requires innovative therapeutic strategies. We developed a magnetic nanoparticle carrying verbascoside (VB-Fe 3 O 4 ) to enhance the bioavailability and antitumor efficacy of VB, a bioactive compound from Rehmannia glutinosa. VB-Fe 3 O 4 demonstrated superior tumor-targeting capabilities, achieving higher drug accumulation compared with free VB. In the human OSCC cell line HSC-3, VB-Fe 3 O 4 markedly induced apoptosis, inhibited proliferation and invasion through IL-6/STAT3 pathway. Mechanistic studies screened out intercellular cell adhesion molecule 1 (ICAM1) as the primary target of VB, with VB-Fe 3 O 4 suppressing IL-6-induced STAT3 phosphorylation. VB-Fe 3 O 4 downregulated metastasis-related genes, such as vascular cell adhesion molecule 1, mucin 1, ezrin, and invasion factor matrix metalloproteinase-9, were markedly decreased by VB-Fe 3 O 4 . VB-Fe 3 O 4 showed greater tumor suppression in OSCC transplanted tumors and experimental metastasis tumors compared with free VB. This nanoplatform synergistically combines precision delivery and molecular targeting, offering a promising treatment for OSCC management.
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Tong Yu,Yeqing Wang,Yi Kong,Jianwei Wang,Hong Yun,Yunchao Wang,Fuqiang Hu,Zhongxin Zhu,Hong Yuan
Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.
研究领域:
药剂学
·
药物递送
·
分子医学
·
纳米技术
·
转化医学
✓ 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）