International Journal of Nanomedicine
·
2025
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IF 6.5
Yixiao Yang,Tao Ye,Fusheng Shang,Dagui Chen,Kai Wang,Shengli He
Introduction Lung cancer, a deadly malignancy, often employs Docetaxel (DTX) as a chemotherapy option. However, DTX non-selective distribution limits its therapeutic effectiveness due to adverse side effects. This study aims to develop novel folate-targeted albumin polyester nanocarriers (FA-DTX-APs) encapsulating DTX for precise delivery, enhancing lung cancer treatment efficacy.Methods FA-DTX-APs were meticulously crafted utilizing the thin-film dispersion technique and subsequently evaluated for their physicochemical characteristics, encapsulation efficiency, and drug release profiles. To assess their biological properties, anti-tumor efficacy, and biosafety in the context of lung cancer, a comprehensive series of hemolysis assays, cellular studies, and animal experiments were conducted.Results FA-DTX-APs exhibit nanovesicle properties with a size of (223.65 ± 6.83) nm, a potential of (26.76 ± 3.15) mV, and encapsulate DTX with high efficiency (96.19 ± 3.27%) and loading capacity (9.75 ± 0.38%). FA-DTX-APs enable tumor-targeted drug delivery and slow release of the drug over a long period of time, with faster release in acidic environments. By efficiently targeting and entering lung cancer cells, FA-DTX-APs effectively hinder cancer growth (P < 0.05), demonstrating superior anti-tumor effects (P < 0.05), biocompatibility and enhanced biological safety (P < 0.05).Conclusion This study introduces FA-DTX-APs, an innovative nanocarrier characterized by exceptional biocompatibility and safety. It successfully targets lung cancer cells to deliver DTX in a sustained, slow-release manner, ensuring prolonged tumor-killing effects. As such, FA-DTX-APs hold immense promise as a novel nanoagent for lung cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
·
IF 3.887
Zili Gu,Minglu Chang,Yang Fan,Yanbin Shi,Guimei Lin
As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200 nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties. Experiments performed in vitro and in vivo on human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced antitumor activity to HT-1080 cells. The results of intravenous administration demonstrated that NGR-modified liposomes can significantly and safely accumulate in tumor tissue in xenografted nude mice. In conclusion, the liposomes constructed hold promise as a safe and efficient drug delivery system for specific tumor treatment.
研究领域:
药学
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
Journal for ImmunoTherapy of Cancer
·
2022
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IF 12.469
Dandan Sheng,Wei Ma,Rui Zhang,Lei Zhou,Qiaodan Deng,Juchuanli Tu,Weilong Chen,Fuchuang Zhang,Nailong Gao,Mengxue Dong,Dong Wang,Fengkai Li,Yin Liu,Xueyan He,Shengzhong Duan,Lixing Zhang,Tong Liu,Suling Liu
Background Although the antitumor efficacy of docetaxel (DTX) has long been attributed to the antimitotic activities, its impact on the tumor microenvironment (TME) has recently gained more attention. Macrophages are a major component of the TME and play a critical role in DTX efficacy; however, the underlying action mechanisms remain unclear. Methods DTX chemotherapeutic efficacy was demonstrated via both macrophage depletion and C–C motif chemokine ligand 3 (Ccl3)-knockout transgenic allograft mouse model. Ccl3-knockdown and Ccl3-overexpressing breast cancer cell allografts were used for the in vivo study. Combination therapy was used to evaluate the effect of Ccl3 induction on DTX chemosensitivity. Vital regulatory molecules and pathways were identified using RNA sequencing. Macrophage phagocytosis of cancer cells and its influence on cancer cell proliferation under DTX treatment were assessed using an in vitro coculture assay. Serum and tumor samples from patients with breast cancer were used to demonstrate the clinical relevance of our study. Results Our study revealed that Ccl3 induced by DTX in macrophages and cancer cells was indispensable for the chemotherapeutic efficacy of DTX. DTX-induced Ccl3 promoted proinflammatory macrophage polarization and subsequently facilitated phagocytosis of breast cancer cells and cancer stem cells. Ccl3 overexpression in cancer cells promoted proinflammatory macrophage polarization to suppress tumor progression and increase DTX chemosensitivity. Mechanistically, DTX induced Ccl3 by relieving the inhibition of cAMP-response element binding protein on Ccl3 via reactive oxygen species accumulation, and Ccl3 then promoted proinflammatory macrophage polarization via activation of the Ccl3–C-C motif chemokine receptor 5–p38/interferon regulatory factor 5 pathway. High CCL3 expression predicted better prognosis, and high CCL3 induction revealed better DTX chemosensitivity in patients with breast cancer. Furthermore, both the Creb inhibitor and recombinant mouse Ccl3 significantly enhanced DTX chemosensitivity. Conclusions Our results indicate that Ccl3 induced by DTX triggers proinflammatory macrophage polarization and subsequently facilitates phagocytosis of cancer cells. Ccl3 induction in combination with DTX may provide a promising therapeutic rationale for increasing DTX chemosensitivity in breast cancer.
研究领域:
肿瘤学
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免疫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
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2024
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IF 2.3
Jun Meng,Bo Yang,Chang Shu,Shuai Jiang
Background Prostate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment. Methods Bioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression. Results FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway. Conclusion This work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
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2018
·Vol. 16
·期 3
·2911-2920
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IF 1.664
Shougang Jiang,Zhiguo Liu,Lei Wu,Yingjie Yuan,Yan Hu,Xingyao Zhang,Liang Wei,Yuangang Zu
Docetaxel (DTX) is currently used as a first‑ or second‑line drug treatment for patients with lung cancer, however, it is less effective for the treatment of patients with bone metastasis of lung cancer. This is primarily due to the fact that docetaxel is nonspecific. In the present study, docosahexaenoic acid (DHA) was selected as a tumor‑targeting ligand, and DHA‑conjugated DTX (DTX‑DHA) was prepared for inhibiting lung cancer metastasis to bone. The anti‑cancer activity assay revealed that DTX‑DHA exhibited a similar antitumor efficacy to DTX in vitro. The maximum tolerated dose of DTX‑DHA was increased compared with that of DTX. The present study results indicated that DTX‑DHA exhibited an improved inhibition efficacy of lung cancer metastasis to bone in comparison with DTX in vivo. Encouragingly, the mean survival time of the DTX‑DHA group (30.60 days) was increased compared with the DTX group (26.10 days; P<0.01). Furthermore, the results of cell migration and osteoclast‑induced formation assays suggested that DTX‑DHA inhibited lung cancer metastasis to bone primarily by affecting lung cancer cell migration. These results indicate that DTX‑DHA may exhibit a potential therapeutic effect against lung cancer metastasis to bone.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2019
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IF 3.829
Weiping Cui,Hanqing Zhao,Chen Wang,Yao Chen,Cong Luo,Shenwu Zhang,Bingjun Sun,Zhonggui He
Self-nanoemulsifying drug delivery system (SNEDDS) have been considered as a promising platform for oral delivery of many BCS (biopharmaceutics classification system) class IV drugs, such as docetaxel (DTX). However, oral chemotherapy with DTX is also restricted by its active P-glycoprotein (P-gp) efflux and hepatic first-pass metabolism. To address these challenges, we developed a novel SNEDDS co-loaded with DTX and cyclosporine A (CsA) to achieve effective inhibition of P-gp efflux and P450 enzyme metabolization, improving oral bioavailability of DTX. The SNEDDS showed uniform droplet size of about 30 nm. Additionally, the prepared SNEDDS exhibited a sequential drug release trend of CsA prior to DTX. The intestinal experiments confirmed that the membrane permeability of DTX was significantly increased in the whole intestinal tract, especially in the jejunum segment. Furthermore, the oral bioavailability of co-loaded SNEDDS was 9.2-fold and 3.4-fold higher than DTX solution and DTX SNEDDS, respectively. More importantly, it exhibited a remarkable antitumor efficacy with a reduced toxicity compared with intravenously administered DTX solution. In summary, DTX-CsA co-loaded SNEDDS is a promising platform to facilitate oral docetaxel-based chemotherapy.
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DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
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2019
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IF 2.442
Juan Cai,Keyang Qian,Xueliang Zuo,Wuheng Yue,Yinzhu Bian,Ju Yang,Jia Wei,Wenying Zhao,Hanqing Qian,Baorui Liu
Docetaxel (TXT) is acknowledged as one of the most important chemotherapy agents for gastric cancer (GC). PI3K/AKT signaling is frequently activated in GC, and its inhibitor LY294002 exerts potent antitumor effects. However, the hydrophobicity of TXT and the poor solubility and low bioavailability of LY294002 limit their clinical application. To overcome these shortcomings, we developed poly(lactic acid/glycolic) (PLGA) nanoparticles loaded with TXT and LY294002. PLGA facilitated the accumulation of TXT and LY294002 at the tumor sites. The in vitro functional results showed that PLGA(TXT+LY294002) exhibited controlled-release and resulted in a markedly reduced proliferative capacity and an elevated apoptosis rate. An in vivo orthotopic GC mouse model and xenograft mouse model confirmed the anticancer superiority and tumor-targeting feature of PLGA(TXT+LY294002). Histological analysis indicated that PLGA(TXT+LY294002) was biocompatible and had no toxicity to major organs. Characterized by the combined slow release of TXT and LY294002, this novel PLGA-based TXT/LY294002 drug delivery system provides controlled release and tumor targeting and is safe, shedding light on the future of targeted therapy against GC.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2021
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IF 6.598
Yuequan Wang,Cong Luo,Shuang Zhou,Xinhui Wang,Xuanbo Zhang,Shumeng Li,Shenwu Zhang,Shuo Wang,Bingjun Sun,Zhonggui He,Jin Sun
Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles (PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxel-fatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cis-trans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2014
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IF 8.312
YuJun Wang,LiJuan Chen,LiWei Tan,Qian Zhao,Feng Luo,YuQuan Wei,ZhiYong Qian
In this study, a composite drug delivery system was developed and evaluated for oral delivery of docetaxel: docetaxel-loaded micelles in pH-responsive hydrogel (DTX-micelle–hydrogel). Docetaxel was successfully loaded in micelles with small particle size of 20 nm and high drug loading of 7.76%, which contributed to the drug absorption in the intestinal tract. The experiments of cytotoxicity on 4T1 cells demonstrated the effective antitumor activity of DTX micelles. Meanwhile, a pH-responsive hydrogel was synthesized and optimized for incorporating the docetaxel micelles. The pH-responsiveness and reversibility of the hydrogel were investigated under the pH conditions of the gastrointestinal tract . Furthermore, the DTX-micelle–hydrogel system showed much quicker diffusion of micelles in simulated intestinal fluid than in simulated gastric fluid, which was mainly caused by the change of pH value. The docetaxel released from the micelle–hydrogel system quite slowly, so it had little influence on the absorption of DTX micelles in small intestine . More important, the pharmacokinetic study revealed that the DTX-micelle–hydrogel significantly improved the oral bioavailability of docetaxel (75.6%) about 10 times compared to DTX micelles, and this increase in bioavailability was probably due to the small intestine targeting release of the pH-responsive hydrogel. Consequently, the oral DTX-micelle–hydrogel system was effective in inhibiting tumor growth in subcutaneous 4T1 breast cancer model, and decreased systemic toxicity compared with intravenous treatment. The apoptosis cells in the immunofluorescent studies and the proliferation-positive cells in the immunohistochemical studies were also consistent with the results. Therefore, the DTX-micelle–hydrogel system might be a promising candidate oral drug for breast cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Lin Li,Xingsheng Di,Shenwu Zhang,Qiming Kan,Hao Liu,Tianshu Lu,Yongjun Wang,Qiang Fu,Jin Sun,Zhonggui He
The therapeutic outcome of glioma treatment is rigorously limited by blood–brain barrier (BBB) and infiltrating growth of glioma. To tackle the dilemma, more and more attentions were focused on developing nutrient transporters-mediated dual-targeted drug delivery system, in one side for BBB penetration, another for intracranial glioma targeting. Herein, Large amino acid transporter 1 (LAT1), overexpressed both on BBB and glioma cells, was selected as a target. Docetaxel-loaded glutamate- d -α-tocopherol polyethylene glycol 1000 succinate copolymer (Glu-TPGS) functionalized LAT1-targeting liposomes (DTX-TGL) were applied to enhance the BBB penetration and glioma therapy. The in vivo results of the fluorescent image indicated that TGL possessed an effective BBB penetration than that of unmodified ones in mice. The LAT1 targeting effcicacy and cell cytotoxicity of TGL were investigated in C6 glioma cells. Compared with unmodified liposomes, a significant higher cellular uptake and cell cytotoxicity was found in TGL treated group. Our results indicated that LAT1-targeting docetaxel-loaded liposome paves up a new direction using LAT1 transporter as a good target in designing brain glioma-targeting nanosystems.
研究领域:
药学
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神经科学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
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2022
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IF 8.663
Ruirui Zhang,Liping Zhong,Xiuli Liu,Xiyu Liu,Qiaoying Chen,Pan Wu,Jian He,Yongmei Li,Yongxiang Zhao,Ziqun Liu,Yan Zu,Yong Huang,Bing Wang
Immunotherapy has made encouraging progress in the field of cancer treatment. Among them, the programmed cell death-ligand 1 (PD-L1) antibody-mediated immunotherapy has stimulated the development of various carrier delivery systems. Inspired by related researchs, in this study, we prepare core-shell structured poly(lactide-co-glycolide) (PLGA) microcapsules as a drug delivery system through microfluidics technology, loaded with PD-L1 aptamers and chemotherapy drug docetaxel. The PD-L1 aptamer loaded in the nuclear layer binds to the PD-L1 molecule produced by tumor cells, blocking the immune checkpoint protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. As a result, phagocytosis of tumor cells is promoted by using lipopolysaccharide (LPS) induced tumor associated macrophages. Furthermore, docetaxel in the shell is further released, inhibiting tumor cell growth as the PLGA microcapsules degrade. More importantly, the combination of PD-L1 aptamers and the chemotherapy drug docetaxel improved the immune response of the tumor. It showed significant anti-tumor activity and reduced systemic side effects in the melanoma model. At present, more and more nucleic acid aptamers as affinity reagents that can replace antibodies have been used to improve tumor treatment. Therefore, this therapeutic strategy provides more possibilities for tumor treatment by combining aptamer molecules with chemotherapy drugs when exploring more effective combination drugs.
研究领域:
癌症治疗
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药物递送系统
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免疫学
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制药学
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产品关联
DOI
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2024
·Vol. 86
·期 1
·e70043
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IF 3.5
Qingqing Li,Yufeng Liu,Yilin Cheng,Huaibao Cao,Kunda Du,Tianyu Zhu,Defeng Xu,Hang Hu
Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug docetaxel (DTX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. In the present research, DTX is condensed with 3-(pyridin-2-yldisulfanyl) propanoic acid via ester bond to obtain the intermediate Py-SS-DTX. Two conjugates GSS-DTX and RGDC-SS-DTX were obtained by conjugation of Py-SS-DTX with glutathione (GSH) and RGDC peptide through a thiol-disulfide exchange reaction. Afterwards, these two peptide–DTX conjugates were characterized by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. The GSS-DTX and RGDC-SS-DTX were further evaluated in terms of drug release, cell cycle inhibition, cell apoptosis, and cytotoxicity. The results show that both the GSS-DTX and RGDC-SS-DTX exhibit reduction-responsive drug release and RGDC-SS-DTX exhibit higher reduction-responsiveness. The in vitro antitumor activity study shows that RGDC-SS-DTX exhibits enhanced G2/M phase arrest, cell apoptosis rate, and cytotoxicity as compared to GSS-DTX and free DTX. Besides, RGDC-SS-DTX shows reduced cytotoxicity on normal cells as compared to free DTX. The RGDC-SS-DTX synthesized in this study represents a novel DTX conjugate to effectively and selectively inhibit tumor cells.
研究领域:
药学
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肿瘤学
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生物化学
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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）