JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Chaochen Shi,Tao Chen,Yingying Li,Wenshuai Li,Yuan Shen,Kehan Cai,Ming Wang,Yazhou Chen
Cell-based delivery holds great promise for advancing cell therapy, but it often faces challenges such as low cell survival rates and immunological rejection during cell injection and circulation. In this study, we develop an alternative approach aimed at engineering cell membranes to produce encapsulated individual mammalian (EIM) cells. The encapsulation shell was formed by catalyzing the reaction of H 2 O 2 with hyaluronic acid-dopamine (HA-DA) on the cell surface using horseradish peroxidase (HRP) enzymes. This protective shell not only protects live mammalian cells from physical stress but also from biological assaults. The individual cell encapsulation system enables the loading of cells with chemotherapy drugs, enhancing their targeting ability towards tumor sites and resulting in over 5.1-fold cell enrichment at metastatic tumors, thereby improving tumor-killing efficacy and reducing metastasis. Overall, the individual cell encapsulation system demonstrates potential for targeted drug delivery to the lungs in the treatment of lung cancer by reducing side effects and enhancing treatment outcomes.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2025
·
IF 16.6
Shang Yan,Li Shuaihu,Xu Tian,Sun Yihua,Li Fei
The CRISPR/Cas9 lentiviral system has emerged as a powerful tool for gene knockout in cancer immunology research. However, the persistent expression of exogenous elements, such as Cas9 and resistance markers, often triggers excessive tumor immune rejection. This can lead to prolonged experimental timelines, increased data variability, biased outcomes, and even experimental failures. To address this challenge, several strategies have been investigated that offer partial solutions, but they have failed so far to comprehensively resolve the issue. In response, we developed the VL-AdCre system, a strategy that enables efficient excision of exogenous expression elements following gene knockout. The VL-AdCre system effectively reduced tumor immune rejection in allograft models, streamlined experimental workflows, and improved the reliability of research outcomes. Overall, this optimized CRISPR/Cas9 lentiviral gene knockout system offers a robust and practical solution for studying gene functions in vivo and advancing immunotherapeutic strategies.
研究领域:
免疫学
·
肿瘤学
·
分子生物学
·
基因编辑
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Jingwen Dong,Chenfei Zhu,Ying Huang,Quanhao Li,Jing Li,Zheng Wang,Yixin Wang,Zhanwei Zhou,Minjie Sun
Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8 + T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.
研究领域:
癌症生物学
·
免疫治疗
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Research
·
2022
·
IF 11.036
Yanhong Wang,Fangchao Xue,Yanzhao Li,Lin Lin,Yeqin Wang,Shanlan Zhao,Xingli Zhao,Yong Liu,Ju Tan,Gang Li,Haoran Xiao,Juan Yan,Hao Tian,Min Liu,Qiao Zhang,Zhaojing Ba,Lang He,Wenyan Zhao,Chuhong Zhu,Wen Zeng
Rapid integration into the host tissue is critical for long-term patency after small diameter tissue engineering vascular grafts (sdTEVGs) transplantation. Neural recognition may be required for host integration and functionalization of the graft. However, immune rejection and inflammation hinder nerve regeneration of sdTEVGs. Here, a CRISPR/dCas9-nanocarrier was used for targeted programming of regulatory T cells (Treg cells) in situ to promote nerve regeneration of sdTEVGs by preventing excessive inflammation. Treg cells and (C-C chemokine receptor) CCR2+ macrophage recruitment occurred after transplantation. The nanodelivery system upregulated ten eleven translocation (TET2) in Treg cells in vitro. Reprogrammed Treg cells upregulated anti-inflammatory cytokines and decreased the proportion of CCR2+ macrophages. IL-6 concentrations decreased to the levels required for nerve regeneration. Implantation of CRISPR/dCas9 nanodelivery system-modified sdTEVGs in rats resulted in Treg cell editing, control of excessive inflammation, and promoted nerve regeneration. After 3 months, nerve regeneration was similar to that observed in normal blood vessels; good immune homeostasis, consistency of hemodynamics, and matrix regeneration were observed. Neural recognition promotes further integration of the graft into the host, with unobstructed blood vessels without intimal hyperplasia. Our findings provide new insights into vascular implant functionalization by the host.
研究领域:
生物医学工程
·
免疫学
·
组织工程
·
分子生物学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
·
2018
·
IF 3.239
Jingjing Du,Yi Zuo,Lili Lin,Di Huang,Lulu Niu,Yan Wei,Kaiqun Wang,Qiaoxia Lin,Qin Zou,Yubao Li
A newly designed hydroxyapatite-polyurethane (HA-PU) composite scaffold was prepared by polymerizing glyceride of castor oil (GCO) with isophorone diisocyanate (IPDI) and HA as fillers. The aim of this study was to determine the effect of HA fillers on the mechanical properties and osteogenesis capacity of the composite scaffolds. The physical and biological properties of the scaffold were evaluated by SEM observation, mechanical testing, cell culture and animal experiments. The results showed that HA fillers enhanced the mechanical properties of PU composite scaffolds such as compressive strength and elastic modulus . The mechanical properties of the scaffolds were seen to increase with increase in HA loading. The compressive strength of composite scaffold with 0 wt%, 20 wt%, 40 wt% of HA was 0.6 ± 0.1 MPa, 2.1 ± 0.1 MPa, and 4.6 ± 0.3 MPa, respectively. In vitro biodegradation studies of scaffolds were carried out. The results showed that all of the scaffolds were susceptible to cholesterol esterase (CE) -catalyzed degradation. HA-PU composite scaffolds exhibited a high affinity to osteoblastic cells and were good template for cell growth and proliferation. When implanted in bone defects of rats, PU scaffolds incorporated HA were biocompatible with the tissue host and had no immune rejection. Moreover, the higher the loading of HA in the composite scaffold, the better chances of osteogenesis. It confirmed that the prepared HA-PU composite scaffolds can be promising candidate for bone repair and bone tissue engineering .
研究领域:
生物材料
·
组织工程
·
生物力学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Zuhan Chen,Huanjing Bi,Jingwen Wang,Ruiyang Ma,Ying Wang,Boqing Dong,Cuinan Lu,Jiale Wang,Yang Li,Jin Zheng,Fang Xie,Xiaoming Ding
Islet transplantation offers a promising therapeutic strategy for type 1 diabetes patients with inadequate glycemic control or severe complications. Islet encapsulation using biocompatible materials presents a potential solution to reduce immune rejection. This study fabricated and characterized Schiff base hydrogels (CMOCs) composed of varying ratios of carboxymethyl chitosan (CMCS) and oxidized carboxymethyl starch (OCMS). CMOCs exhibited desirable mechanical properties, injectability, self-healing properties, antibacterial properties, biocompatibility, and controlled-release capabilities. CMOC3, with the highest CMCS content, was selected for loading Fasudil and further islet encapsulation experiments. In vitro studies demonstrated that CMOC3 and CMOC3-Fasudil hydrogel (CMOC3-Fas) not only supported islet survival and insulin secretion but also increased insulin bioavailability through chelating the zinc ions from the insulin hexamers. CMOC3-Fas exhibited pro-angiogenic and anti-inflammatory properties, and effectively reduced islet cell death under hypoxic conditions. Finally, transplantation of islets encapsulated within CMOC3-Fas achieved prolonged normoglycemia and increased body weight in diabetic mice. This study demonstrates the synergistic protective effect of Schiff-base hydrogel co-delivering fasudil for islet encapsulation, potentially paving the way for improved islet transplantation therapy in type 1 diabetes.
研究领域:
生物材料
·
组织工程
·
再生医学
·
糖尿病研究
·
药物递送
·
生物工程
·
免疫学
·
移植医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2024
·
IF 4.2
Lisha Liu,Beiyuan Zhang,Xianggui Wu,Gang Cheng,Xiaopeng Han,Xiaofei Xin,Chao Qin,Lei Yang,Meirong Huo,Lifang Yin
Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.
研究领域:
肿瘤学
·
纳米技术
·
免疫疗法
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Haofei Li,Yulian Shang,Qi Feng,Yang Liu,Junlin Chen,Hua Dong
Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.
研究领域:
生物医学工程
·
组织工程
·
糖尿病研究
·
细胞治疗
✓ 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）