Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Binbin Liang,Tao Deng,Jinping Li,Xueliang Ouyang,Weidan Na,Dawei Deng
The rational design of theranostic systems are critical for addressing challenging issues associated with cancers. Toward this objective, the multifunctional biomimetic superparticle, termed as DOX-QDs-Lip@M, which can specifically deliver drug to tumor and synergistically monitor their therapeutic effects, was fabricated. Initially, anticancer drug doxorubicin hydrochloride (DOX) and imaging agent quaternary quantum dots (QDs) were loaded into the hydrophilic core region and hydrophobic chamber of liposome by self-assembly method, respectively. The integrated nanostructure can greatly increase the fluorescence intensity of signal unit and tremendously improve the diagnostic sensitivity. Subsequently, the biomimetic DOX-QDs-Lip@M was constructed by fusing and coating the isolated macrophage membranes on the surface of liposome, which can consequently extend the circulation of the whole blood and effectively target the tumor sites. Moreover, the naturally formed biofilm can stabilize the artificial liposome structure, which can prevent the leakage of the loaded materials in the liposome. These integrated properties endow the biomimetic DOX-QDs-Lip@M with improved tumor imaging and anti-metastasis treatment in living systems.
研究领域:
肿瘤学
·
生物医学工程
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Xuemin Shen,Zhenfeng Liu,Junhui Li,Dongmei Wu,Meng Zhu,Lufeng Yan,Guizhu Mao,Xingqian Ye,Robert J. Linhardt,Shiguo Chen
Low molecular weight heparins (LMWHs) are currently used as an anticoagulant agent since unfractionated heparin (UFH) can cause serious adverse drug reactions. LMWHs are commercially prepared using different methods such as nitrous acid cleavage and β-elimination under strong reaction conditions or with harsh chemicals, which may cause the saccharide units within the polysaccharide backbone to be decomposed and noticeably modified. This study demonstrates an effective method for depolymerizing heparin via the production of large amounts of free radicals from H 2 O 2 /ascorbic acid and ultrasonic power; this results in highly pure products because ascorbic acid can decompose during the reaction, which is different from the previously reported H 2 O 2 /Cu 2+ method. The reaction conditions—including concentration of ascorbic acid, reaction temperature and intensity of ultrasonic power—were investigated and optimized. We found that the degradation behavior of heparin in this combined physicochemical process conformed to first-order reaction kinetics . The chemical composition and structures of different LMWHs were analyzed. The results showed the primary structure and sulfate esters were well preserved after the depolymerization , the major repeat units are (1–4)-linked glucosamine and iduronic acid . The further in vitro assays indicated that the LMWHs produced by H 2 O 2 /ascorbic acid with ultrasonic power have an anti-metastatic effect in A549 cells, which suggested the LMWHs rapidly prepared in this physicochemical way have a potential for anti-tumor metastatic function.
研究领域:
药理学
·
生物化学
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DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2024
·
IF 3.1
An Le,Yu Yang,He Long,Xiao Xu,Li Pengcheng
There are numerous therapeutic applications for ginsenoside Rb1 (GRb1), the primary saponin derived from ginseng root. According to earlier research, ginsenoside Rb1 causes apoptosis and reduces the cell cycle. Its adverse effects, especially those on the development of the embryo, still need to be thoroughly studied. A host’s lifestyle choices, including smoking, drinking too much alcohol, using tobacco products, and having an HPV infection, can increase the risk of oral squamous cell carcinoma (OSCC), one of the most prevalent malignancies of the oral cavity. To address this challenge, this investigation focuses on the design of GRb1 for treating OSCC. In vitro cytotoxicity studies confirmed that GRb1 was more effective in PCI-9A and PCI-13 cells, with reduced toxicity in non-cancerous cells. Further verification of cellular morphology was achieved through various biochemical staining methods. The mechanism of cell death was investigated by Annexin V-FITC and PI methods. Additionally, the antimetastatic attributes of GRb1 have been evaluated using both migration scratch and Transwell migration assays, which have collectively revealed excellent antimetastatic potential. The DNA fragmentation of the PCI-9A and PCI-13 cells was assessed using a comet assay. Ginsenoside Rb1 improved ROS levels and caused mitochondrial membrane potential alterations and DNA damage, which resulted in apoptosis. OSCC administration significantly reduced the levels of SOD, GSH, GPx, and CAT, increasing the levels of PCI-9A and PCI-13 cells, while GRb1 improved this situation. Therefore, we propose that Ginsenoside Rb1 could be an alternative therapeutic strategy for OSCC therapy.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 12
·1516
·
IF 4.9
Cailian Chen,Jinying Liu,Hongbo Zhang,Hongrui Zhang,Yanhui Liang,Qilian Ye,Wei Shen,Haibin Luo,Ling Guo
Background: Lung cancer is an aggressive disease with rapid progression and a high rate of metastasis, leading to a significantly poor prognosis for many patients. While chemotherapy continues to serve as a cornerstone treatment for a large proportion of lung cancer patients, expanding preclinical and clinical evidence indicates that chemotherapy may promote tumor metastasis and cause side effects.Methods: We develop an injectable bait-and-hook hydrogel (BH-gel) for targeted tumor cell eradication, which embedded doxorubicin liposomes as cytotoxic agents and CXCL12 as a chemoattractant to capture and kill tumor cells. The hydrogel backbone was formed through covalent cross-linking between PVA and borax. In vitro, we investigated tumor recruitment and the antitumor effects in A549 cells. In vivo, we explored the anti-metastatic and antitumor activities against lung cancer.Results: BH-gel retained CXCL12 within its three-dimensional porous architecture for gradual release, effectively recruiting tumor cells. In contrast, blank hydrogel failed to achieve this. After encapsulation in BH-gel, the therapeutic efficacy of doxorubicin liposomes for tumor eradication was markedly improved, significantly reducing metastatic tumor presence to near-undetectable levels, while also resulting in notable reductions in cardiotoxicity and hepatotoxicity. Notably, BH-gel adhered well to tissues and exhibited exceptional electrical conductivity, which may be further developed into a real-time tumor monitoring system, facilitating timely therapeutic adjustments.Conclusions: BH-gel utilizes CXCL12 as a bait to recruit and entrap tumor cells in a three-dimensional porous matrix and subsequently kill them with embedded doxorubicin liposomes, thereby tackling the issue of metastatic spread. This bait-and-hook strategy has significant implications for the field of anti-metastasis medicine and shows considerable potential for clinical application.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 6
·期 3
·458-468
·
IF 4.543
Yu Sun,Yuling Bao,Xue Jiang,Songwei Tan,Mingxing Yin,Conglian Yang,Liping Zhou,Zhiping Zhang
Physical properties, such as surface charge, of nanomedicines play a crucial role in their in vivo behaviors, which could eventually determine the tumor inhibition effect. Although drug delivery systems with positive charge are effective for cell internalization, this property is universally applicable to the lack of selectivity of both tumors and normal tissues, resulting in rapid blood clearance and undesired side effects. By employing charge-reversible strategies, the dilemma can be overcome and enhanced cellular uptake, prolonged circulation time and high biocompatibility can be realized. Here, we constructed Vitamin E-based micelles with charge-reversible property for the delivery of the antineoplastic agent paclitaxel. In the slightly acidic tumor microenvironment, the micelles converted from negative to positive charge due to the cleavage of the pH-sensitive bond, leading to enhanced cellular uptake and subsequently enhanced drug release. The micelles demonstrated improved antitumor efficiency both in vitro and in vivo and improved anti-metastasis effect in 4T1 orthotopic tumor model compared with those of clinically formulated Taxol and non-sensitive micelles. Besides, the micelles showed high biocompatibility and reduced side effects. Overall, these findings highlight that the micelles with charge-reversible property have great potential for cancer therapy in clinic.
研究领域:
药学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Haifeng Sun,Dinglingge Cao,Hao Wu,Huan Liu,Xue Ke,Tianyuan Ci
Tumor metastasis is the primary obstacle in cancer treatment and is always the leading cause of human death. And heparin and its derivatives are potential anti-metastatic agents with good biocompatibility. In this work, low molecular weight heparin (LMWH) based LMWH-Cholesterol (LHC) conjugates were prepared for intravenous delivery of doxorubicin (DOX). The DOX/LHC nanoparticles (DOX/LHC NPs) exhibited a spherical shape with a mean diameter of 135.5 ± 2.2 nm and had a longer circulation time than that of DOX. The in vitro results confirmed that the DOX/LHC NPs was more effectively taken up by 4T1 cells and showed a stronger anti-metastatic effect by cell invasion and cell migration compared with DOX. Meanwhile, DOX/LHC NPs also exhibited superior anti-metastatic effects in the pulmonary metastasis model compared with other groups. The reason may be account for the synergistic effect between the cytotoxic drug of DOX and its drug carrier of LMWH based nanoparticles, which is capable of anti-metastatic and anti-angiogenic efficiency. Thus DOX/LHC nanoparticles could be a promising anti-metastatic drug delivery system for postoperative chemotherapy.
研究领域:
药学
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2024
·
IF 3.5
Linming Li,Yan Chen,Ming Zhang,Suying Li,Shuaiqi Feng,Yan-Qin He,Ning Zhang,Zhifang Liu,Meifeng Liu,Qing-Peng Wang
Protective autophagy is a promising target for antitumor drugs exploration. A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI of 44.2% against 4T1 tumors in vivo and possessed rather lower toxicity than cisplatin. Notably, it exhibited satisfactory antimetastatic activities toward lung pulmonary metastasis models with inhibition rate of 49.6%, which was obviously more potent than CDDP (21.6%). Mechanism detection revealed that it caused serious DNA damage and upregulated the expression of γ-H2AX and p53. More importantly, the incorporation of autophagy inhibitor HCQ endowed platinum(IV) complex with potent autophagy impairing properties by perturbing lysosomal function in tumor cells, which promoted apoptosis synergistically with the DNA injury. Then, the impaired autophagy further led to the suppression of hypoxia and inflammation in tumor microenvironment by downregulating ERK1/2, HIF-1α, iNOS, caspase1 and COX-2. Adaptive immune response was improved by inhibiting immune checkpoint PD-L1, and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Jiaojiao Chen,Shaoxia Wang,Huiyuan Zhang,Huixiang Li,Fei Wang,Yinglin Wang,Quan Zhao
Chemotherapy proves to be a successful method in treating primary breast cancer. Ironically, some commonly used chemotherapeutics may promote lung metastasis by increasing the activity of activating transcription factor 3 (ATF3). Thus, it is necessary to inhibit tumor metastasis while improving the anti-tumor effect of anti-cancer drugs. Herein, using curcumol (CUR) that possesses both anti-tumor and anti-metastasis activities as a model drug, we designed the nanogels based on temperature-responsive self-assembly and glutathione-triggered disassembly to address the abovementioned conflicts. Briefly, the copolymers (H-SS-P) were synthesized by coupling poly (N-isopropylacrylamide) onto hyaluronic acid (HA) via a disulfide bond-containing linker cystamine dihydrochloride . Copolymers could self-assemble into regular spherical nanogels at 37 °C with a 40-nm particle size for PNIPAAm's thermosensitivity. Hydrophobic CUR could be automatically entrapped into the core of nanogels. The H-SS-P@CUR nanogels could release drugs quickly upon exposure to the reductive tumor microenvironment . The superior efficacy of H-SS-P@CUR on inhibiting tumor growth was validated through assays both in vivo and in vitro . Moreover, nanogels may better down-regulate the expression of ATF3 protein by enhancing the cell uptake and tumor targeting of CUR, thereby significantly improving the anti-metastasis effect of CUR. This work not only proposed a novel strategy to simplify the preparation process of nanogels but also achieved effective drug delivery with enhanced anti-cancer and anti-metastasis effects.
研究领域:
药学
·
癌症研究
·
纳米技术
·
药物递送系统
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jing Tao,Yuan Yao,Minyi Huang,Jiahui Wu,Jiayan Lyu,Qiuyi Li,Lian Li,Yuan Huang,Zhou Zhou
The cytoskeleton facilitates tumor cells invasion into the bloodstream via vasculogenic mimicry (VM) for “attack”, and protects cells against external threats through cytoskeletal remodeling and tunneling nanotubes (TNTs) for “defense”. However, the existing strategies involving cytoskeleton are not sufficient to eliminate tumor metastasis due to mitochondrial energy supply, both within tumor cells and from outside microenvironment. Here, considering the close relationship between cytoskeleton and mitochondria both in location and function, we construct a nano-platform that combats the “attack” and “defense” of cytoskeleton in the cascading metastasis. The nano-platform is composed of KF Csk @LIP and KT Mito @LIP for the cytoskeletal collapse and mitochondrial dysfunction. KF Csk @LIP prevents the initiation and circulation of cascading tumor metastasis, but arouses limited suppression in tumor cell proliferation . KT Mito @LIP impairs mitochondria to trigger apoptosis and impede energy supply both from inside and outside, leading to an amplified effect for metastasis suppression. Further mechanisms studies reveal that the formation of VM and TNTs are seriously obstructed. Both in situ and circulating tumor cells are disabled. Subsequently, the broken metastasis cascade results in a remarkable anti-metastasis effect. Collectively, based on the nano-platform, the cytoskeletal collapse with synchronous mitochondrial dysfunction provides a potential therapeutic strategy for cascading tumor metastasis suppression.
研究领域:
肿瘤学
·
纳米技术
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
CANCER GENE THERAPY
·
2022
·Vol. 29
·期 8
·1217-1227
·
IF 5.854
Wang Zhiwei,Li Mingxing,Liu Yuanfeng,Qiao Zhentao,Yang Ling,Liu Bo,Bai Tao
Autophagy is the predominant self-eating catabolic pathway activated in response to nutrient starvation and hypoxia within the microenvironment of varied malignancies, including hepatocellular carcinoma (HCC). SQSTM1/p62 links its cargos to autophagosomes for degradation, and reportedly acts as a contributor for hepatocarcinogenesis. Five GEO gene microarrays identified corticotropin releasing hormone (CRH) binding protein (CRHBP) as a significantly downregulated gene in HCC (log2 Fold change < −3 and p < 0.001), and an earlier human interactome study indicated that CRHBP may interact with p62. This study aimed to explore (1) the role of CRHBP in HCC development, and (2) whether p62-mediated autophagy was responsible for low CRHBP expression within HCC tissue. Following functional experiments first revealed an anti-proliferative, anti-metastatic, and anti-angiogenic role of CRHBP in HCC cells (Huh-7, Li-7 and HCCLM3) and xenografts. CRHBP negatively regulated cyclin B2 expression, and dissociated cyclin B2-CDK1 complex in HCC cells, thereby leading to cell cycle arrest at G2 phase. To simulate HCC microenvironment in vitro, Huh-7 cells were incubated in Earle’s Balanced Salt Solution (nutrient starvation) or exposed to 1% O 2 (hypoxic exposure). In addition to activating autophagy, nutrient starvation and hypoxic exposure also induced CRHBP degradation. Interestingly, CRHBP was demonstrated as a novel cargo targeted by p62 for degradation in autophagosomes. Blocking autophagy with 3-MA, chloroquine or siSQSTM1 prevented CRHBP degradation in HCC cells. Collectively, our study uncovers a role for CRHBP in retarding HCC development, reducing cyclin B2 expression and impairing cyclin B2-CDK1 interaction. CRHBP downregulation in HCC may attribute to p62-mediated autophagy.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Lie-Feng Ma,Li−Li Xu,Ling-Jie Yuan,Xi Yang,Rui Wu,Shu-Min Bao,Yi-Li Chen,Hong-Liang Duan,Luo Fang,Hua-Jun Zhao,Zha-Jun Zhan
Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure−activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Hao Wu,Yuan Luo,Dongmei Xu,Xue Ke,Tianyuan Ci
The standard-of-care chemotherapy is important in the treatment of osteosarcoma and bone metastastic tumors. However, the efficacy is limited by the specific physiological environment of the bone. Thus, developing an efficient antitumor and anti-metastasis chemotherapeutic formulation is desired for treatment of bone tumors. Herein, we utilized the alendronate (ALN) and low molecular weight heparin (LMWH) modified liposomes to deliver the antitumor drug doxorubicin (DOX), where traditionally-believed non-active drug carrier, targeting moiety could also exhibit biological functions and realize anti-tumor and anti-metastasis efficiency synergistically with the antitumor drug. Specifically, ALN could serve as the bone targeting moiety and the therapeutic agents of anti-osteoporosis. LMWH could enhance the blood circulation time of liposomes and exhibit anti-metastasis efficiency. Besides characterization of typical physiochemical properties of the delivery system, both the orthotopic osteosarcoma model and bone metastasis cancer model were adopted to evaluate the in vivo efficacy. The results proved this system could remarkably suppress tumor growth and inhibit tumor metastasis.
研究领域:
药学
·
肿瘤学
·
药物递送系统
✓ 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）