JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2019
·Vol. 38
·期 1
·1-18
·
IF 5.646
Zheng Ning,Liu Weiqun,Li Bifei,Nie Huifang,Liu Jian,Cheng Yunlong,Wang Jichuang,Dong Haiyan,Jia Lee
Background Sorafenib is approved as a standard therapy for advanced hepatocellular carcinoma (HCC), but its clinical application is limited due to moderate therapeutic efficacy and high incidence of acquired resistance resulted from elevated levels of SDF-1/CXCR4 axis induced by prolonged sorafenib treatment. We previously demonstrated metapristone (RU486 metabolite) as a cancer metastatic chemopreventive agent targeting SDF-1/CXCR4 axis. Therefore, we hypothesized that combining sorafenib with metapristone could synergistically suppress cell proliferation, enhance anti-cancer activity and repress potential drug resistance. Methods Changes in cellular CXCR4 expression by metapristone were analyzed by RT-PCR and western blotting. Effect of combining sorafenib with metapristone on cell viability was examined by MTT assay; combination index value was calculated to evaluate the synergistic effect of combined therapy. To overcome poor pharmacokinetics and reduce off-target toxicity, CXCR4-targeted nanoparticles (NPs) were developed to co-deliver sorafenib and metapristone into CXCR4-expressing HCC in vitro and in vivo; cell proliferation, colony formation and apoptosis assays were conducted; nude mice bearing HCC xenograft were used to examine effects of this therapeutic approach on HCC progression. Results Here we showed metapristone significantly reduced CXCR4 expression in HCC. Combinatory chemotherapy of sorafenib with metapristone synergistically suppressed HCC proliferation and resistance. CXCR4-targeted PEGylated poly (lactic-co-glycolic acid) NPs conjugated with LFC131 (a peptide inhibitor of CXCR4), could deliver more sorafenib and metapristone into HCC via specific recognition and binding with transmembrane CXCR4, and resulted in the enhanced cytotoxicity, colony inhibition and apoptosis by regulating more Akt/ERK/p38 MAPK/caspase signaling pathways. Co-delivery of sorafenib with metapristone by the LFC131-conjugated NPs showed prolonged circulation and target accumulation at tumor sites, and thus suppressed tumor growth in a tumor xenograft model. Conclusions In conclusion, co-delivery of sorafenib and metapristone via the CXCR4-targeted NPs displays a synergistic therapy against HCC. Our results suggest combinational treatment of chemotherapeutics offer an effective strategy for enhancing the therapeutic efficacy on carcinoma, and highlight the potential application of ligand-modified tumor-targeting nanocarriers in delivering drugs as a promising cancer therapeutic approach.
研究领域:
肿瘤学
·
药学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Green Processing and Synthesis
·
2023
·Vol. 12
·期 1
·
IF 4.3
Xin Zhang,Xutong Zhu,Lifa Huang,Zupeng Chen,Yuchen Wang,Yajun Liu,Ruihan Pan,Ling Lv
Tanshinone IIA has a potential therapeutic effect on cerebral ischemia/reperfusion injury (CIRI). In this study, tanshinone IIA was encapsulated in poly(lactic- co -glycolic acid)-block-poly (ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) nanoparticles, and its therapeutic efficacy on CIRI was investigated. Morphology and dynamic light scattering analyses were performed to identify and optimize nano-formulations. A drug release test was conducted using the dialysis method. The cytotoxic effect of tanshinone IIA on human neuroblastoma cells (SH-SY5Y) and brain endothelial capillary cells (hCMEC/D3) was measured using the MTT assay. The protective effect of PLGA-PEG-COOH-encapsulated tanshinone IIA against CIRI was evaluated in oxygen and glucose deprivation/reoxygenation-induced SH-SY5Y/IR cells and middle cerebral artery occlusion (MCAO) rats. Results showed that PLGA-PEG-COOH-encapsulated tanshinone IIA promoted viability and inhibited apoptosis of SH-SY5Y/IR cells ( P < 0.01). Moreover, PLGA-PEG-COOH-encapsulated tanshinone IIA facilitated the invasion of SH-SY5Y/IR cells and repressed inflammation in MCAO rats ( P < 0.01). Noteworthy, PLGA-PEG-COOH-encapsulated tanshinone IIA combined with angiopep-2 peptide presented a better inhibitory effect on CIRI than tanshinone IIA alone ( P < 0.01). Angiopep-2 peptide contributes to traversing blood–brain barrier by recognizing lipoprotein-related protein expressed in the brain capillary endothelial cells. In conclusion, PLGA-PEG-COOH-encapsulated tanshinone IIA plus angiopep-2 peptide holds promising therapeutic potential toward CIRI.
研究领域:
药学
·
神经科学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Li Piao,Peng Xiang,Yangyang Zhou,Wei Zhao,Ting Yang,Shan Xia,Guanghui Gao,Kexin Chen,Dan Li
Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.
研究领域:
肿瘤学
·
药剂学
·
生物材料
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2019
·Vol. 37
·期 6
·548-559
·
IF 2.804
Xu Wei-Ke,Tang Jing-Yu,Yuan Zhang,Cai Cai-Yun,Chen Xiao-Bin,Cui Shu-Quan,Liu Peng,Yu Lin,Cai Kai-Yong,Ding Jian-Dong
Bacterial infection is a very troublesome issue in wound treatment, which stimulates exudate formation and severely delays the healing process. Herein, a thermogelling dressing system composed of two triblock copolymers of poly(D,L-lactic acid- co -glycolic acid)- b -poly(ethylene glycol)- b -poly(D,L-lactic acid- co -glycolic acid) (PLGA-PEG-PLGA) with different block lengths was developed to deliver teicoplanin (TPN), a glycopeptide antibiotic, for cutaneous wound repair. The TPN-loaded thermogel was a free-flowing sol at room temperature and formed a semi-solid gel at physiological temperature. In vitro studies demonstrated that the TPN-loaded thermogel system exhibited desired tissue adhesiveness and realized the sustained release of TPN in a fast-followed-slow manner for over three weeks. Furthermore, a full-thickness excision wound model in Sprague-Dawley (SD) rats was constructed to assess the efficacy of TPN-loaded thermogel formulation. Gross and histopathologic observations implied that treatment with the thermogel formulation reduced inflammation response, promoted disposition of collagen, enhanced angiogenesis, and accelerated wound closure and maturity of SD rats. The combination of the bioactivity of TPN and the acidic nature of the thermogel matrix was responsible for such an enhanced wound healing process. Consequently, the TPN-loaded PLGA-PEG-PLGA thermogel is a good candidate of wound dressing for full-thickness excision wound healing.
研究领域:
药学
·
生物医学工程
·
伤口护理
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药物递送系统
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Shengnuo Fan,Yuqiu Zheng,Xuan Liu,Wenli Fang,Xiaoyu Chen,Wang Liao,Xiuna Jing,Ming Lei,Enxiang Tao,Qiulan Ma,Xingmei Zhang,Rui Guo,Jun Liu
Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.
研究领域:
神经科学
·
药学
·
纳米技术
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2023
·
IF 6
Junwei Xu,Yi Cui,Meili Liu,Zitong An,Kun Li,Xuenan Gu,Ping Li,Yubo Fan
The incidence of cancer and other diseases continues to increase, posing a serious threat to human health. Drug delivery systems using bionic red blood cell (RBC)-like microparticles (MPs) as drug carriers have been extensively studied, as they are considered ideal carriers due to the unique shape. However, most methods of preparing multifunctional RBC-like MPs are complicated, and the cell affinity and therapeutic effect of MPs prepared using simple electrospray are unsatisfactory. In this context, hydrophilicity-enhanced and magnetic-luminescent bifunctional RBCs-like Janus MPs [Fe 3 O 4 @poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA/PLGA]//[NaYF 4 :Eu 3+ @PLGA-PEG-PLGA/PLGA] were successfully prepared by one-step double-needle electrospray method. The physical and chemical properties, such as morphology, particle size, structure, and thermal stability of the MPs, were studied. The addition of block polymer PLGA-PEG-PLGA was found to enhance the hydrophilicity of the MPs, promote cell spreading and adhesion proteins (focal adhesion kinase and Paxillin) mRNA expressions of human umbilical vein endothelial cells, significantly improving the cell affinity. The results also demonstrated that RBC-like MPs exhibited excellent magnetic and enhanced luminescent properties, making them a promising candidate for various biomedical applications, including drug delivery systems, magnetic targeting, bio-imaging, and fluorescent tracing.
研究领域:
生物医学工程
·
材料科学
·
药学
·
细胞生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Xin Jin,Qiang Fu,Zehui Gu,Zhenhai Zhang,Huixia Lv
The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA–PEG–PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment . The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.
研究领域:
药学
·
癌症研究
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qingyu Lu,Wenhao Gao,Zhenzhen Chen,Zhihong Liu,Jie Wang,Lingjun Zeng,Xiaomu Hu,Enqin Zheng,Qian Zhang,Hongtao Song
Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy. Therefore, modulating energy metabolism pathways and inhibiting ATP production may be a potential strategy to reverse MDR. Herein, we developed a PTX-ATO-QUE nanoparticle (PAQNPs) based on a PLGA-PEG nanoplatform capable of loading the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor atovaquone (ATO), the glycolysis inhibitor quercetin (QUE), and the chemotherapeutic drug paclitaxel (PTX) to reverse MDR by inhibiting energy metabolism through multiple pathways. Mechanistically, PAQNPs could effectively inhibit the OXPHOS and glycolytic pathways of A2780/Taxol cells by suppressing the activities of mitochondrial complex III and hexokinase II (HK II), respectively, ultimately decreasing intracellular ATP levels in tumor cells. Energy depletion can effectively inhibit cell proliferation and reduce P-gp activity, increasing the chemotherapeutic drug PTX accumulation in the cells. Moreover, intracellular reactive oxygen species (ROS) is increased with PTX accumulation and leads to chemotherapy-resistant cell apoptosis. Furthermore, PAQNPs significantly inhibited tumor growth in the A2780/Taxol tumor-bearing NCG mice model. Immunohistochemical (IHC) analysis of tumor tissues revealed that P-gp expression was suppressed, demonstrating that PAQNPs are effective in reversing MDR in tumors by inducing energy depletion. In addition, the safety study results, including blood biochemical indices, major organ weights, and H&E staining images, showed that PAQNPs have a favorable in vivo safety profile. In summary, the results suggest that the combined inhibition of the two energy pathways, OXPHOS and glycolysis, can enhance chemotherapy efficacy and reverse MDR in ovarian cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Xinrui Li,Jing Su,Zul Kamal,Pengcheng Guo,Xinyi Wu,Lina Lu,Hongbing Wu,Mingfeng Qiu
Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur–OL–NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG–PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG–PBLG) and OL–PEG–PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur–OL–NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, in vivo pharmacokinetic studies also showed that Cur–OL–NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL–NPs as carriers of Cur had a promising future in nasal drug delivery system.
研究领域:
药剂学
·
神经科学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 8
·2001-2009
·
IF 3.641
Ma Jun,Yu Da-Hai,Zhao Di,Huang Teng,Dong Min,Wang Ting,Yin Hai-Tao
Radiotherapy is an effective anti-cancer therapy for patients with non-small cell lung cancer (NSCLC), however, the prognosis is unsatisfactory owing to radio-resistance and toxicity. It is crucial to improve radiotherapy efficacy. Ag nanoparticles (NPs) and ginsenoside Rg3 (Rg3) exerted
antitumor and radio-sensitization effects. Therefore, we investigated whether poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG)-Rg3-Ag will function as a noninvasive, tracing, radiotherapy sensitizer. The morphology of NPs was visualized with transmission electron microscopy (TEM).
The drug loading content, encapsulation efficiency, and cumulative drug release of Rg3 was determined by HPLC. Cellular uptake of NPs in A549 and SPCA-1 was measured by immunostaining. The radio-sensitization effect of PLGA-PEG-Rg3-Ag in vitro was determined in A549 by detecting proliferation,
colony formation, and apoptosis with CCK-8, clonogenic survival assay, and flow cytometry, while in vivo was determined in nude mice by testing the body weight and tumor volume. PLGA-PEG-Rg3-Ag exerted radio-sensitization effect by reducing cell proliferation and colony formation while
enhancing cell apoptosis in A549; reduced tumor volume in nude mice. PLGA-PEG-Rg3-Ag exhibits radio-sensitization effects in NSCLC.
研究领域:
肿瘤学
·
药剂学
·
放射治疗学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Huang Yaxian,Wu Jinyan,Zhan Chi,Liu Rong,Zhou Zhaocai,Huang Xin,Tian Yaguang,Lin Zhengmei,Song Zhi
The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.
研究领域:
牙科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2011
·
IF 1.396
Jianian Chen,Shaoshun Li,Qi Shen,Huijuan He,Yi Zhang
The aim of this paper is to evaluate the cellular uptake of vincristine sulfate-loaded poly(lactic-co-glycolic acid)–polyethylene glycol (PLGA–PEG) nanoparticles with the folic acid modification (PLGA–PEG–folate NPs). PLGA–PEG–folate NPs were prepared using a water–oil–water emulsion solvent evaporation method. The particle size, surface morphology, drug encapsulation efficiency, and the drug release behavior were investigated. The NPs exhibited a biphasic drug release with a moderate initial burst followed by a sustained release profile. Internalization of the NPs labeled with coumarin- 6 by MCF-7 (Michigan Cancer Foundation-7) human breast cancer cells was quantitatively measured by microplate reader, and qualitatively analyzed by fluorescent microscopy and confocal laser scanning microscopy. The results showed PLGA–PEG–folate NPs achieved significantly higher cellular uptake in the folic acid receptor overexpressed MCF-7 cells, compared to PLGA–mPEG NPs without the folic acid modification. Due to the enhanced cellular uptake, PLGA–PEG–folate NPs displayed the highest cytotoxicity. Judged by IC50 after 24 h culture, the therapeutic effects of the drug formulated in the NPs with surface modification could be 1.52 times, 3.91 times higher than that of PLGA–mPEG NPs and free vincristine sulfate, respectively.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）