JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 2.713
Qi Liu,Di Zhao,Xiaojie Zhu,Huili Chen,Yue Yang,Jiaqiu Xu,Qing Zhang,Ali Fan,Ning Li,Chaorui Guo,Ying Kong,Yang Lu,Xijing Chen
The purpose of this study was to develop a nanocarrier system for codelivery of paclitaxel (PTX) and piperlongumine (PL) and investigate the therapeutic potential of improving efficacy and reducing toxicity. PTX and PL were formulated into poly lactic-co-glycolic acid and D-α-tocopheryl polyethylene glycol succinate via organic solvent evaporation method. The average diameter was 117.1 ± 1.9 nm , and the zeta potential was −43.25 ± 2.76 mV. PL facilitated the cellular uptake of PTX, and the increased cytotoxicity was similarly displayed. The formulation with the PTX/PL concentration ratio at 1:200 showed the best antitumor activity , the IC 50 of PTX were 5.10 ± 0.08 nM in HepG2 cells, and 3.79 ± 1.01 nM in Michigan Cancer Foundation–7 cells. Correspondingly, the combination index was 0.79 and 0.76. Furthermore, intracellular uptake of PTX toward HepG2 cells in coencapsulated nanoparticles was significantly more than free solution. In addition, the antitumor effect of PTX/PL-PTNPs in the HepG2 xenograft tumor model suggested that the nanoparticles showed a higher antitumor efficacy with reduced toxicity to other tissues compared with free PTX. In summary, the results indicated that PTX/PL-PTNPs processed well characteristics and enhanced its therapeutic efficacy; thus, this delivery system could be clinically effective for treatment of cancers.
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
PLoS One
·
2014
·Vol. 9
·期 9
·e106900
·
IF 3.534
Fei Qiao,Hanqing Cong,Xuefei Jiang,Rongxiang Wang,Junmei Yin,Dan Qian,Zhunian Wang,Peter Nick
Cephalotaxus hainanensis , an endangered plant, is known to contain several metabolites with anti-cancer activity. Despite its clinical impact, the alkaloid metabolism of this species has remained largely uncharacterized. The potential of Cephalotaxus for metabolic engineering of medically interesting compounds has, so far, not been exploited, due to the almost complete lack of molecular information. We have therefore performed a high throughput RNA-seq analysis and assembled the transcriptome de novo . Raw reads comprising 4.3 Gbp were assembled de novo into 39,416 unique sequences (unigenes) with a mean length of 1,089.8 bp and a total assembly size of 45.8 Mbp, which equals to more than 50 times the number of Cephalotaxaceae sequences currently deposited in the GenBank (as of August 2013). As proof of principle for medically interesting pathways, gene fragments related to paclitaxel biosynthesis were searched and detected. To verify their functionality, the metabolic product paclitaxel, and its precursor baccatin III, were identified in the leaves of C. hainanensis by HPLC, and shown to be induced by MeJA. This finding demonstrates exemplarily the potential of the annotated transcriptome as information resource for the biotechnological exploitation of plant secondary metabolism.
研究领域:
植物学
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遗传学
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分子生物学
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药理学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 15
·3024-3031
·
IF 4.726
Weipu Zhu,Ying Wang,Xia Cai,Guangyu Zha,Qiaojie Luo,Rui Sun,Xiaodong Li,Zhiquan Shen
Paclitaxel-loaded reduction-responsive core-crosslinked micelles were prepared in situ in aqueous media via “click” chemistry. An amphiphilic block copolymer with multiple pendant azide groups was first synthesized through the controlled ring-opening copolymerization of ε-caprolactone (CL) and 5,5-dibromomethyl trimethylene carbonate (DBTC) in the presence of methoxy poly(ethylene glycol) (mPEG) as a macroinitiator, followed by azidation. This amphiphilic block copolymer could self-assemble into micelles and paclitaxel (PTX) could be encapsulated into the micellar core to form PTX-loaded micelles, which were core-crosslinked in situ by propargyl dithiopropionate via “click” chemistry, to develop a reduction-responsive polymeric drug delivery system. The in vitro release studies revealed the minimized release of PTX under physiological conditions, whereas a burst release of PTX was observed in response to reductive conditions. The core-crosslinked micelles displayed efficient cell-uptake and reduction-responsive drug release due to the nanoscale diameter and splitting of disulfide bonds under a reductive environment, which was confirmed by confocal laser scanning microscopy using Nile red as a fluorescent probe. This kind of polymeric nano-carrier with excellent biocompatibility and quick reduction-response opens a new avenue to intracellular anticancer drug delivery.
研究领域:
药剂学
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聚合物化学
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纳米技术
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癌症研究
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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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
✓ 已验证
产品关联
DOI
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
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肿瘤学
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药物递送系统
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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
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材料科学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2015
·Vol. 294
·期 1
·135-143
·
IF 1.865
Guo Yanzhu,Zhang Li,Li Haiming,Han Ying,Zhou Jinghui,Wang Xiaohui
A series of α-tocopherol succinate-conjugated hydroxyethyl cellulose (HEC-TOS) polymers were synthesized in this study. The weight percentages of TOS in HEC-TOS were varied from 15 to 36 % by adjusting the weight ratios of TOS to HEC from 1:4 to 5:2. The HEC-TOS polymers exhibited typical properties of amphiphilic polymers and were able to self-assemble into spherical nanomicelle in aqueous solution as revealed by TEM. The micelle sizes and critical micelle concentrations (CMC) of HEC-TOS conjugates were correlated with their molecular structures and were in the range of 24.5–115.1 nm and 16–99 μg/ml, respectively. Paclitaxel (PTX) was encapsulated into the core of HEC-TOS micelle by sonication-dialysis method. The highest loading concentration of PTX in micelle was 315 mg/ml, which was about 50 times higher than that in water (6 mg/l). The in vitro study showed that PTX was continuously released from PTX-loaded micelle in phosphate buffered saline (PBS) medium for 108 h.
研究领域:
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Chunxi Qian,Bandar Al-Hamyari,Xiaofei Tang,Bo Hou,Shuaibo Yang,Guifang Zhang,Huijuan Lv,Zhigang Yang,Zhaohui Wang,Yanbin Shi
Having benefited from the combination of different therapeutic modalities, functionalized nanoplatforms with synergistic strategies have aroused great interest in anticancer treatment. Herein, an engineered, a biodegradable hollow mesoporous organosilica nanoparticle (HMON)-based nanoplatform was fabricated for photothermal-enhanced chemotherapy of tumor. For the first time, we demonstrated that HMONs could serve as nanocarriers for co-delivering of both the paclitaxel and photothermal agent new indocyanine green (IR820), denoted as Paclitaxel/IR820@ HMONs-PEG. The as-prepared nanosystem exhibited a high paclitaxel-loading capacity of 28.4%, much higher than most paclitaxel-loaded nanoformulations. Furthermore, incorporating thioether bonds (S-S) into the HMONs’ framework endowed them with GSH-responsive biodegradation behavior, leading to the controllable release of drugs under a tumor reducing microenvironment, and hindered the premature release of paclitaxel. Upon being irradiated with an NIR laser, the obtained co-delivery nanosystem exhibited great photothermal properties generated from IR820. The fabricated nanocomposites could significantly suppress tumor growth under NIR laser irradiation, as validated by in vitro and in vivo assessments. Combined with outstanding biocompatibility, the constructed nanosystem holds great potential in combinational antitumor therapy.
研究领域:
纳米技术
·
癌症治疗
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材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
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
·
药学
·
癌症研究
·
药物递送系统
✓ 已验证
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
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Yixin Dong,Kun Yang,Zicheng Xu,Xun Li,Fei Wang,Yu Zhang
The application of drug delivery systems based on ferritin nanocarrier has been developed as a potential strategy in cancer therapy. The limited permeability of ferritin remains a challenge for drug penetration into the deeper tumor tissues. CendR peptides have been reported to bear tumor-specific penetration by recognizing neuropilin (NRP-1) receptor that overexpressed on a wide range of cancer cells. Herein, we modified CendR peptide L(RGERPPR), its retro-inverso peptide D(RPPREGR), and inverso peptide D(RGERPPR) on the outer surface of human H chain ferritin by sulfhydryl-maleimide coupling reaction. Approximately 45 paclitaxel (PTX) molecules could be loaded into each ferritin inner cavity by a thermal-triggered method at a specific ionic strength. The penetration ability of three peptide-modified ferritin constructs showed that D(RGERPPR)-modified HFtn was able to be engulfed by A549 and MCF-7 tumor cells and spheroids at the highest level. Due to the dual-targeting effect of ferritin and modified peptides, the PTX-loaded nanocomposites could effectively enter the cells with high expression of TfR1 and NRP-1 receptors and enhanced the cytotoxicity against tumor cells. Remarkably, H-D(RGE)-PTX displayed a superior tumor growth suppression efficacy in A549 tumor-bearing nude mice. The inverso CendR peptide-modified HFtn nanocarrier was first generated and could provide an effective dual-targeting platform for treatment of cancers.
研究领域:
药学
·
癌症研究
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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