Nanomedicine-Nanotechnology Biology and Medicine
·
2016
·
IF 5.671
Xin Jin,Mengying Li,Lifang Yin,Jianping Zhou,Zhenhai Zhang,Huixia Lv
Tyroservatide (YSV) is a tripeptide that has been approved for clinical testing, as a new anticancer drug . In the current study, YSV-stearic acid (YSV-SA) was inserted into the surface of d -alpha-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS)-modified paclitaxel (PTX) liposomes (TP-Lip) to form YSV-conjugated TP-Lip (TYP-Lip). Both in vivo imaging and in vitro cell uptake analysis indicated that these modifications could increase tumor-targeting and cell uptake of the liposomes. Optimal antitumor effects were achieved via tail vein injections of TYP-Lip in MB-231 tumor-bearing nude mice . Overall, the formed TYP-Lip not only achieved a synergistic anticancer effect through YSV and PTX, but also improved tumor-targeting and exhibited further antitumor capabilities. These results indicated that combining biological (YSV) and chemotherapeutic (PTX) agents is an efficient combinatorial delivery strategy for enhanced tumor targeting and synergistic antitumor effects.
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
Frontiers in Bioengineering and Biotechnology
·
2026
·
IF 5.8
Mingmei Ding,Jiaqi Song,Chen Zhao,Xiyun Yang,Yuehan Ouyang,Zhining Zhuo,Xiaobang Chen,Ruitian Zhu,Xiangqin Wang,Tianhao Yu,Xiumei Tian,Fanwen Yang
Introduction Benign central airway stenosis (BCAS) remains difficult to manage because restenosis is frequently driven by fibroproliferative responses after intervention. To address this challenge, we developed a long-acting paclitaxel (PTX)-eluting silicone airway stent that integrates hydrophilic modification, a porous drug-reservoir structure, and ultrasound-responsive release. Methods Three hydrophilic modifiers (PEG-600, HM-530, and PVP-K17) were screened to improve matrix wettability and drug diffusivity. Coating thickness, pore formation, and cyclic ultrasound stimulation were further optimized. Drug release behavior, release kinetics, and mechanical performance were characterized systematically. In vitro cytocompatibility and anti-fibrotic activity were evaluated using L929, HFL-1, BEAS-2B, and HBE135 cells. Results PVP-K17-modified porous stents combined with cyclic ultrasound showed the optimal release profile, achieving 22.85% cumulative PTX release over 90 days while retaining mechanical integrity. Drug release was well fitted by a comprehensive kinetic model (R 2 > 0.99) incorporating pore-forming (Kt) and ultrasound-enhancement (St) coefficients. Extracts of the modified silicone material met ISO 10993-5 cytocompatibility criteria, and PTX treatment selectively inhibited fibroblasts while showing relatively limited effects on epithelial cell viability. Discussion These findings establish an integrated design framework for hydrophilic-modified, ultrasound-activated drug-eluting silicone airway stents that combine sustained local drug delivery, mechanical reliability, and selective anti-fibroproliferative activity.
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Kang Xiong,Yan Zhang,Qian Wen,Jia Luo,Yun Lu,ZhouXue Wu,BiQiong Wang,Yue Chen,Ling Zhao,ShaoZhi Fu
Multi-drug chemotherapy has been one of the most popular strategies for the treatment of malignant tumors, and has achieved desirable therapeutic outcomes. The objective of the present study is to develop biodegradable PCEC nanoparticles (NPs) for the co-delivery of paclitaxel (PTX) and curcumin (CUR), and investigate the antitumor effect of the drug delivery system (DDS: PTX-CUR-NPs) against breast cancer both in vitro and in vivo. The prepared PTX-CUR-NPs had a small size of 27.97 ± 1.87 nm with a low polydispersity index (PDI, 0.197 ± 0.040). The results exhibited slow release of PTX and CUR from the DDS without any burst effect. Further, the PTX-CUR-NPs displayed a dose-dependent cytotoxicity in MCF-7 cells with a higher apoptosis rate (64.29% ± 1.97%) as compared to that of free drugs (PTX + CUR, 34.21% ± 0.81%). The cellular uptake study revealed that the drug loaded PCEC polymeric nanoparticles were more readily uptaken by tumor cells in vitro. To evaluate the in vivo anti-tumor effect, the PTX-CUR-NPs were intravenously administered to BALB/c nude mouse xenografted with MCF-7 cells and the results exhibited significant inhibition of tumor growth with prolonged survival time and reduced side effect when compared with free drugs (PTX + CUR). Moreover, the administration of PTX-CUR-NPs treatment led to lower Ki67 expression (p < 0.05), and enhanced TUNEL positivity (higher apoptosis, p < 0.01) in tumor cells as compared to other treatment groups, suggesting the therapeutic efficacy of the DDS. Altogether, the present study suggests that the DDS PTX-CUR-NPs could be employed for the effective treatment of breast cancers in near future.
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
BIOMATERIALS
·
2020
·
IF 10.317
Kaiyuan Wang,Hao Ye,Xuanbo Zhang,Xia Wang,Bin Yang,Cong Luo,Zhiqiang Zhao,Jian Zhao,Qi Lu,Haotian Zhang,Qiming Kan,Yongjun Wang,Zhonggui He,Jin Sun
Metastasis is closely associated with high breast cancer mortality. Although nanotechnology-based anti-metastatic treatments have developed rapidly, the anti-metastasis efficiency is still far from satisfactory, mainly due to the poor recognition of circulating tumor cells (CTCs) in blood. Herein, we developed an exosome-like sequential-bioactivating prodrug nanoplatform (EMPCs) to overcome the obstacle. Specifically, the reactive oxygen species (ROS)-responsive thioether-linked paclitaxel-linoleic acid conjugates (PTX-S-LA) and cucurbitacin B (CuB) are co-encapsulated into polymeric micelles , and the nanoparticles are further decorated with exosome membrane (EM). The resulting EMPCs could specifically capture and neutralize CTCs during blood circulation through the high-affinity interaction between cancer cell membrane and homotypic EM. Following cellular uptake, EMPCs first release CuB, remarkably blocking tumor metastasis via downregulation of the FAK/MMP signaling pathway . Moreover, CuB obviously elevates the intracellular oxidative level to induce a sequential bioactivation of ROS-responsive PTX-S-LA. In vitro and in vivo results demonstrate that EMPCs not only exhibit amplified prodrug bioactivation, prolonged blood circulation, selective targeting of homotypic tumor cells, and enhanced tumor penetration, but also suppress tumor metastasis through CTCs clearance and FAK/MMP signaling pathway regulation. This study proposes an integrated approach for mechanism-based inhibition of tumor metastasis and manifests a promising potential of programmable-bioactivating prodrug nanoplatform for cancer metastasis inhibition .
研究领域:
纳米技术
·
癌症生物学
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Yawei Du,Zhi Wang,Tao Wang,Wei He,Wenya Zhou,Man Li,Chen Yao,Xinsong Li
The microtubule inhibitor paclitaxel (PTX) is used to treat a wide range of solid tumors. Due to the poor aqueous solubility of PTX, a continuous demand for safe, efficient PTX formulations with improved antitumor activity exists. Here, we report a novel form of redox-sensitive paclitaxel (PTX)-encapsulated liposomes based on the previously developed disulfide phosphatidylcholine (SS-PC). PTX-loaded stealth liposomes (PTX/SS-LP) composed of SS-PC, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG2000 (DSPE-PEG2000), and cholesterol were prepared using the reverse-phase evaporation method. The characterization of the PTX/SS-LP liposomes using dynamic light scattering and transmission electron microscopy confirmed their uniform particle size and typical unilamellar vesicle structure with an average bilayer thickness of approximately 4 nm. Changes in the size and morphology as well as the rapid release of PTX triggered by the addition of dithiothreitol revealed the redox sensitivity of PTX/SS-LP. Finally, evaluations in MCF-7 and A549 cells in vitro and in BALB/c mice in vivo revealed the improved anticancer efficiency, biodistribution, and safety of PTX/SS-LP compared with those of Taxol and nonredox-sensitive PTX/LP. In conclusion, PTX/SS-LP displays a redox-responsive release of paclitaxel with improved antitumor activity and has great potential as a next-generation stealth liposomal PTX delivery system.
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
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Qingzhi Lv,Jincheng Yang,Ruoshi Zhang,Zimeng Yang,Zhengtao Yang,Yongjun Wang,Youjun Xu,Zhonggui He
Prostate cancer (PCa) is the most prevalent cancer among men in the United States and remains the second-leading cause of cancer mortality in men. Paclitaxel (PTX) is the first line chemotherapy for PCa treatment, but its therapeutic efficacy is greatly restricted by the nonspecific distribution in vivo. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most PCa cells, and its expression level increases with cancer aggressiveness, while being present at low levels in normal cells. The high expression level of PSMA in PCa cells offers an opportunity for target delivery of nonspecific cytotoxic drugs to PCa cells, thus improving therapeutic efficacy and reducing toxicity. PSMA has high affinity for DUPA, a glutamate urea ligand. Herein, a novel DUPA–PTX conjugate is developed using DUPA as the targeting ligand to deliver PTX specifically for treatment of PSMA expressing PCa. The targeting ligand DUPA enhances the transport capability and selectivity of PTX to tumor cells via PSMA mediated endocytosis. Besides, DUPA is conjugated with PTX via a disulfide bond, which facilitates the rapid and differential drug release in tumor cells. The DUPA–PTX conjugate exhibits potent cytotoxicity in PSMA expressing cell lines and induces a complete cessation of tumor growth with no obvious toxicity. Our findings give new insight into the PSMA-targeted delivery of chemotherapeutics and provide an opportunity for the development of novel active targeting drug delivery systems for PCa therapy.
研究领域:
肿瘤学
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2020
·
IF 4.545
Huanhuan Xu,Litian Wang,Boya Shi,Lihong Hu,Chunxia Gan,Ya Wang,Zemin Xiang,Xuanjun Wang,Jun Sheng
Caffeine (1,3,7-trimethylxanthine) is a xanthine alkaloid found in a number of dietary products consumed worldwide, such as coffee, tea, and soft beverages, and is known to act as a modifying agent for cytotoxic chemotherapeutic drugs. Studies have shown that caffeine reduces the cytotoxic effects of paclitaxel and inhibits paclitaxel-induced apoptosis; however, the underlying mechanism remains unclear. Here, we investigated whether caffeine inhibits the antitumor activity of paclitaxel via down-regulation of α-tubulin acetylation. In vitro studies, involving MTT assay, wound-healing assay, cell apoptosis assay, and western blotting analysis of A549 and HeLa cells, were performed. A549 and HeLa cell-based xenografts were established, and western blotting and immunohistochemical staining were performed for in vivo studies. The results showed that caffeine promoted the growth of cancer cells treated with paclitaxel. Additionally, caffeine enhanced migration ability, inhibited apoptosis, and decreased the acetylation of α-tubulin in paclitaxel-treated cancer cells. Furthermore, caffeine decreased the inhibitory effect of paclitaxel on tumor growth through down-regulation of α-tubulin acetylation in vivo . Taken together, these findings demonstrate that caffeine inhibits the anticancer activity of paclitaxel via down-regulation of α-tubulin acetylation, suggesting that patients receiving treatment with taxanes, such as paclitaxel, should avoid consuming caffeinated beverages or foods.
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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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2019
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IF 3.845
Yang Yihua,Wang Zhe,Peng Ying,Ding Jinsong,Zhou Wenhu
Micelles are highly attractive nano-drug delivery systems for targeted cancer therapy. While they have been demonstrated to significantly alleviate the side-effects of their cargo drugs, the therapy outcomes are usually suboptimal partially due to ineffective drug release and endosome entrapment. Stimulus-responsive nanoparticles have allowed controlled drug release in a smart fashion, and we want to use this concept to design novel micelles. Herein, we reported pH-sensitive paclitaxel (PTX)-loaded poly (ethylene glycol)-phenylhydrazone-dilaurate (PEG-BHyd-dC12) micelles (PEG-BHyd-dC12/PTX). The micelles were spherical, with an average particle size of ∼135 nm and a uniform size distribution. The pH-responsive properties of the micelles were certified by both colloidal stability and drug release profile, where the particle size was strikingly increased accompanied by faster drug release as pH decreased from 7.4 to 5.5. As a result, the micelles exhibited much stronger cytotoxicity than the pH-insensitive counterpart micelles against various types of cancer cells due to the hydrolysis of the building block polymers and subsequent rapid PTX release. Overall, these results demonstrate that the PEG-BHyd-dC12 micelle is a promising drug delivery system for cancer therapy.
研究领域:
纳米技术
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药学
·
癌症研究
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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
NEW JOURNAL OF CHEMISTRY
·
2016
·Vol. 40
·期 12
·9923-9929
·
IF 3.277
Meng-Xia Chen,Ting Li,Song Peng,Dan Tao
The encapsulation of paclitaxel (PTX) using amphiphilic calixarene (SC4-C6) is an attempt to improve its water solubility. The optimized nanocapsules were successfully prepared by a thin film hydration method where an organic phase containing the mixture of PTX and SC4-C6 (molar ratio of 1 : 10) was dispersed by probe sonication for 30 s into an aqueous phase. The optimized formulation of PTX loaded amphiphilic calix[4]arene nanocapsules had an average particle size of 206 ± 14 nm and an encapsulation efficiency of 82.65 ± 2.54%. Transmission electron micrographs demonstrated the sphere shape of the PTX loaded amphiphilic calix[4]arene formulation without obvious agglomeration. In vitro drug release experiments clarified the obvious sustained release behaviors of the PTX loaded amphiphilic calix[4]arene formulation compared to commercial Taxol. Furthermore, the PTX loaded SC4-C6 formulation revealed improved PTX induced cytotoxicity in human cervical cancer cell culture experiments in contrast to Taxol. The nanocapsules assembled from amphiphilic calixarenes obtained in this work displayed a desired narrow size range with acceptable drug loading and sustained release behaviors, which are beneficial for their potential application as an anti-cancer drug delivery vehicle.
研究领域:
药物化学
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纳米医学
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肿瘤学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Yan Jiang,Xiuzhen Wang,Xin Liu,Wei Lv,Hongjuan Zhang,Mingwan Zhang,Xinrui Li,Hongliang Xin,Qunwei Xu
Glioblastoma multiforme (GBM) presents one of the most lethal brain tumor with a dismal prognosis. And nanodrug delivery system (nano-DDS) have raised a lot of concern, while the conventional nanoformulations addressed many limitations, especially the low drug loading capacity and poor stability in vivo. Herein, we proposed PTX prodrug (PTX-SS-C18) conjugate self-assembled nanoparticles (PSNPs) functionalized with Pep-1, glioma homing peptide, to overcome the blood brain tumor barrier (BBTB) via interleukin 13 receptor α2 (IL-13Rα2)-mediated endocytosis for targeting GMB. This nanocarrier was with ultrahigh drug loading capacity (56.03%) and redox-sensitivity to the up-expression of glutathione in glioma tumors. And compared with PEG-PSNPs, Pep-PSNPs could significantly enhance cellular uptake in U87MG cells via IL-13Rα2-mediated endocytosis. Enhanced cytotoxicity of Pep-PSNPs against U87MG cells and BCEC cells pretreated with glutathione monoester (GSH-OEt) confirmed that this nanosystem was sensitive to reduction environment, and there was significant difference between targeting and nontargeting groups in MTT assay. Real-time fluorescence image of intracranialU87MG glioma-bearing mice revealed that Pep-PSNPs could more efficiently accumulate at tumor site and improve the penetration. Furthermore, the ex vivo fluorescence imaging and corresponding semiquantitative results displayed that the glioma fluorescence intensity of Pep-PSNPs group was 1.74-fold higher than that of nontargeting group. Pep-PSNPs exhibited remarkable antiglioblastoma efficacy with an extended median survival time. In conclusion, Pep-PSNPs had a promising perspective as a targeting drug delivery system of PTX for glioma treatment.
研究领域:
药物递送系统
·
癌症治疗
·
神经科学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yujie Zhang,Zhongyuan Guo,Zhonglian Cao,Wenxi Zhou,Yu Zhang,Qinjun Chen,Yifei Lu,Xinli Chen,Qin Guo,Chao Li,Donghui Liang,Tao Sun,Chen Jiang
Targeted delivery and accumulation of chemotherapeutics to tumor sites is in high demand and extremely challenging for anticancer therapy. Studies show that albumin is actively recruited into tumor tissue overexpressing albumin-binding proteins including secreted protein acidic and rich in cysteine (SPARC) and gp60. Herein, a novel redox-responsive paclitaxel-loaded micelle system with the modification of ABD035, which specifically and strongly binds to albumin, is designed to combine the strengths of albumin and micelles together for antitumor drug biomimetic delivery. The ABD035-modified micelle has a strong binding response to albumin and co-localization of BODIPY-labeled ABD035-modified micelle and SPARC is observed in tumor tissues. Furthermore, the ABD035-modified micelle significantly improves the therapeutic effect in the animal model bearing triple negative breast cancer by increasing drug accumulation in tumor tissue, enhancing cell uptake efficiency, rapidly releasing prototype drug under intracellular reductive conditions and increasing tumor cell apoptosis. These results together vote the biomimetic delivery of ABD035-modified micelle as a promising strategy for cancer therapy.
研究领域:
药理学
·
肿瘤学
·
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
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Jianwei Bai,Yunan Zhang,Longqi Chen,Huijun Yan,Chunhong Zhang,Lijia Liu,Xiaodong Xu
In this study, novel molecularly imprinted polymer (MIP) microparticles containing methacryl polyhedral oligomeric silsesquioxane (M-POSS) were synthesized through the RAFT precipitation polymerization (RAFTPP) method using paclitaxel (PTX) as the templates. During the course of this investigation, methacrylic acid (MAA) was used as the functional monomer, while ethylene glycol dimethacrylate (EGDMA) was utilized as a cross-linker. The effects of different molar ratios of M-POSS on the microparticles were characterized. The obtained MIP microparticles were confirmed by FT-IR and TGA-DSC. The results of SEM showed regular spherical-shaped MIP microparticles with diameters around 170–490 nm. The PTX loading quantity was closely correlated with the content of M-POSS, and the MIP microparticles showed a satisfactory affinity to PTX with high drug loading (17.1%) and encapsulation efficiency (85.5%). Moreover, these MIP microparticles were sensitive to pH, and consequently the release rates of PTX at pH 5 were much faster than those at pH 7 due to the acid cleavage of the hydrogen bonds. In addition, the results from release experiments of the MIP microparticles showed a very slow and controlled release of PTX, which heralded promising potential as a carrier for PTX delivery in cancer therapy.
研究领域:
药学
·
材料科学
·
肿瘤学
✓ 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）