INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
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IF 4.845
Yi Chen,Qianming Du,Ying Zou,Qianqian Guo,Jing Huang,Ling Tao,Xiangchun Shen,Jianqing Peng
High metastasis is responsible for the failure in the treatment of melanoma . Chemoimmunotherapy has shown conspicuous inhibition effects not only on the growth of tumor in situ, but also on the metastasis to distant organs. Given that the indoleamine-2,3 dioxygenase (IDO) overexpressed in the microenvironment of tumor leads to the immune escape, the combination of chemotherapeutic drug and IDO inhibitor might be a promising chemoimmunotherapy. Besides, the hematogenous metastasis mediated by platelets was supposed to be blocked by the heparin (HP). Therefore, a drug delivery system with all these elements involved might be a potential treatment for melanoma. Here, we developed a pH-sensitive liposomal dual-delivery system for doxorubicin (DOX) and epacadostat (EPA) with HP coated (HP/LDE). It was confirmed to enhance cytotoxicity and apoptosis , reverse the platelets-activated epithelial mesenchymal transformation (EMT) and prevent the invasion and migration in vitro . After systemic administration , HP/LDE provided the optimum anti-metastasis effect on the melanoma. The results of evaluation on DC maturation, CD8 + cytotoxic T lymphocytes (CTLs) activation and T cell mediated cytotoxicity were consistent in vitro and in vivo . Taken together, our study established a functional liposomal dual-delivery system with ideal anti-metastasis efficacy on melanoma.
研究领域:
肿瘤学
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药理学
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免疫学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
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IF 10.6
Liu Yang,Ding Lei,Chen Gaojie,Wang Peiyuan,Wang Xinghuan
Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu 2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H 2 O 2 ) catalyzed by intracellular GOx into oxygen (O 2 ), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract
研究领域:
生物医学工程
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纳米技术
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癌症生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2022
·Vol. 27
·期 5
·160
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IF 3.115
Yuzhu Cao,Keqin Lu,Yawen Xia,Yufei Wang,Aiyun Wang,Yang Zhao
Background: The interactions between platelets and tumor cells are well-known to play important roles in the progression of malignant tumors. Danshensu, a main water-soluble component of Salvia miltiorrhiza, can resist platelet aggregation and exert significant anti-tumor effects on various types of tumors. However, whether Danshensu could inhibit the progression of malignant tumors by suppressing the activities of platelets had not been reported. Methods: The effects of Danshensu on the platelet activity and epithelial-mesenchymal transformation (EMT)-like invasive phenotype of SW620 colon cancer cells were assessed by stimulating with the supernatants from co-cultured platelets and SW620 cells with direct contact (SCP). The expression and secretion of proteins were determined by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin and eosin (H&E) staining was performed to analyzed the histopathology of tumor tissues and immunohistochemical staining was conducted to examine the protein expression in tumors. Results: Co-incubation of SW620 cells with platelets directly or SCP both generated long spindle-shaped invasive phenotype. Pretreatment of platelets with Danshensu (25 μM) inhibited the morphological changes of SW620 cells induced by SCP, which was associated with the inhibitory effects of Danshensu on platelet secretion. Danshensu diminished the secretion of a list of biological factors in SCP, including interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) that are all involved in tumor cell EMT and chemoresistance. Moreover, Danshensu up-regulated the expression of E-cadherin but down-regulated the levels of N-cadherin and Vimentin, resulting in the repression of SW620 cell migration. It was also shown that Danshensu enhanced the sensitivity of SW620 cells to oxaliplatin by suppressing the expression of MDR1. Furthermore, Danshensu could not only reduced the growth of subcutaneous tumors and liver metastasis that induced by SCP, but also down-regulated the expression of MDR1 in vivo. Mechanistic studies revealed that Danshensu suppressed the activation of the TGF-β/Smad signaling pathway. Conclusions: Danshensu attenuated EMT-like characteristics and chemoresistance by inhibiting secretion capability of platelets and activation of the TGF-β/Smad signaling pathway, suggesting that it may be optimized to be a therapeutic agent for fighting against colon cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Jiarun Sun,Youping Gong,Yuchen He,Jianwei Cui,Haifeng Chen,Nanyan Kang,Yixie Wu,Jiahao Hui,Huipeng Chen,Rougang Zhou,Huifeng Shao,Ying Yu
Vascularized tissue models represent a pivotal approach for enhancing the accuracy of clinical drug prediction by recapitulating the in vivo microenvironment. However, replicating the structural complexity, functional integration, and long-term stability inherent in native vascular tissues remains a significant challenge within the tissue engineering field. Herein, a novel strategy employing aqueous-embedded coaxial bioprinting is proposed. By optimizing the rheological compatibility between alginate-collagen (Alg-Col) bioink and xanthan gum-collagen (XG-Col) support bath, the high-fidelity and efficient fabrication of vascularized tissue models is achieved. Utilizing a triaxial nozzle, synchronous deposition of a bilayered vascular construct containing human umbilical vein endothelial cells (HUVECs) and human lung fibroblasts (HLFs) is performed directly within a tumor cell (human lung adenocarcinoma PC-9 cell line)-laden support bath, resulting in the construction of a perfusable vascularized lung cancer tissue model. Drug assessment revealed significantly lower sensitivity of PC-9 cells to erlotinib within the 3D vascularized model compared to controls. In addition to the physical barrier effect, the vascularized microenvironment activated cancer cell survival pathways primarily through paracrine signaling from endothelial cells and fibroblasts. Gene expression analysis further demonstrated the induction of epithelial-mesenchymal transition (EMT) in the vascularized model. This integrated platform more accurately recapitulates in vivo drug diffusion kinetics and resistance mechanisms, thereby providing an innovative preclinical platform for enhanced anticancer drug screening.
研究领域:
组织工程
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生物打印
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癌症研究
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药物开发
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再生医学
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微环境建模
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4890-4906
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IF 6.6
Jianhao Liu,Xiaoman Xu,Yanying Li,Jingxia Xu,Ruogang Zhao,Siwei Liu,Jingliang Wu,Li Zhang,Bo Zhang
Comprehensively regulating the TME is now regarded as a promising approach for cancer treatment. Herein, a novel “three-in-one” effect is presented for simultaneously killing tumor cells, inhibiting the EMT of CAFs, and improving immune responses. In this study, bortezomib (BTZ) is selected for the treatment of breast cancer; it has multiple pharmacological mechanisms for killing tumor cells through the NF-κB signaling pathway, inhibiting the activity of CAFs by activating caspase-3, and enhancing the function of CD8+ T cells by regulating the expression of immune-stimulating factors. To improve the druggability of BTZ in solid tumors, BTZ-loaded lipid/glycocholic acid mixed micelles (BTZ-LGs) were prepared to verify the “three-in-one” effect in killing tumor cells, inhibiting CAFs, and improving immune responses. In the present work, BTZ-LGs were verified to show enhanced in vitro cytotoxicity in both 4T1 cells and 4T1/NIH3T3 co-cultured cells, as well as a superior in vivo treatment effect in different tumor-bearing mouse models. Additionally, BTZ-LGs could regulate the expression of α-SMA, caspase-3, E-cadherin, and N-cadherin, indicating their good inhibiting ability on both tumor cells and CAFs. More importantly, immunological analysis revealed that BTZ-LGs promoted the expression of the immunostimulatory factor IL-2 in tumor tissues, activated anti-tumor T cells, and overcame tumor-induced CD8+ T cell dysfunction. All these findings suggest that BTZ-LGs can achieve a “three-in-one” effect in terms of killing tumor cells, suppressing CAFs, and improving immune responses. This simple and multi-effective therapeutic strategy offers a promising approach for cancer therapy.
研究领域:
癌症治疗
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药学
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免疫学
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细胞生物学
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分子生物学
✓ 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）