JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
·
IF 5.062
Wang Yin,Liu Tian,Shenchun Wang,Dezhen Zhang,Shengrong Guo,Meidong Lang
This study reported a co-delivery system of paclitaxel (PTX) and doxorubicin (DOX) based on a functionalized poly(ϵ-caprolactone) (FC) conjugated with folate (FA) and PTX prodrug (FA-FC-PTX). PTX was conjugated to pendant carboxyl groups of FC by esterification, and FA was modified to PEG block of FC. The release behaviors of DOX and PTX from the micelles of FA-FC-PTX loaded with DOX (FA-FC-PTX/DOX) were obviously different. DOX was almost completely released in the initial 24 h, while a small amount of PTX was only released for 24 h, and continued to be released for 7 days. The cellular uptake results showed that FA-FC-PTX/DOX could be more effectively internalized by 4T1 cell than the non-folate drug-loaded micelles. In vitro cytotoxicity assays demonstrated that FA-FC-PTX/DOX revealed synergistic effect in inhibiting the proliferation of 4T1 mouse breast cancer cells. Cell apoptosis assays showed that FA-FC-PTX/DOX had the highest apoptosis rate in all drug formulations, indicating that it had high ability to induce cell apoptosis. Furthermore, it was found that FA-FC-PTX/DOX exhibited better inhibition effect on 4T1 tumor growth compared with free PTX/DOX combination or non-folate drug-loaded micelles and there was no obvious side effect on the 4T1 tumor-bearing mice. Thus, this work provides a promising drug co-delivery system for targeted therapy of breast cancer.
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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DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2020
·
IF 7.489
Rui Xia,Qing Pei,Jian Wang,Zhanfeng Wang,Xiuli Hu,Zhigang Xie
Redox stimulus responsive drug delivery systems have been widely investigated and proved to be promising prospects for efficient cancer therapy due to the abnormal high level of reactive oxygen species and glutathione in tumor microenvironment. Herein, three paclitaxel dimers (named as PTX 2 -R, R = S, Se and Te) bridged with alkyl sulfide, selenide or telluride are synthesized. These dimers can self-assemble into stable uniform nanoparticles (named as PTX 2 -R NPs, R = S, Se and Te) with impressively high drug loading. As expected, sulfur/selenium/tellurium bonds exhibit different redox responsiveness, thereby affecting the drug release and cytotoxicity. Of note, tellurium bridged paclitaxel dimer shows ultra-sensitivity to hydrogen peroxide, which rapidly cleaves into two paclitaxel under the subsequent dithiothreitol stimulation. Our findings provide deep insight into the redox sensitivity of chalcogenide elements and offer the rational design strategies to biologically redox condition for programmed drug release.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
International Journal of Biological Sciences
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2022
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IF 10.75
Li Zhang,Linyu Zhu,Xiaohan Yao,Xiaohan Lou,Jiajia Wan,Xixi Duan,Longze Pan,Anqi Li,Zhuoyu Gu,Ming Wang,Fazhan Wang,Zhihai Qin
Chemotherapeutic drugs have been successfully used to treat several cancers, including melanoma. However, metastasis occasionally occurs after chemotherapy. Here, we reported that paclitaxel (PTX) treatment for B16F10 tumour in mice led to an enhanced lymphatic metastasis of the melanoma cells, although a significant inhibition of tumour growth at the injection site was observed. Further study demonstrated that PTX upregulated the expression of C-C chemokine receptor type 7 (CCR7) in B16F10 cells, enhancing their migration through the activation of JNK and p38 signalling pathways. Loss of CCR7 or blockade of C-C motif chemokine ligand 21 (CCL21)/CCR7 axis abolished the pro-migration effect of PTX on B16F10 melanoma cells. Importantly, combination of PTX and CCR7 mAb could simultaneously delay the tumour growth and reduce the lymphatic metastasis in B16F10 melanoma. The blockade of CCL21/CCR7 axis may collectively serve as a strategy for lymphatic metastasis in some melanoma after chemotherapy.
研究领域:
肿瘤学
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免疫学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 5
·期 4
·849-857
·
IF 4.872
Lingjie Wu,Ming Wu,Xinyi Lin,Xiaolong Zhang,Xiaolong Liu,Jingfeng Liu
Highly efficient accumulation of nanoscaled theranostic agents in a tumor site is crucial for cancer diagnosis and therapy. In this study, we designed a drug-loaded charge-switchable nanohybrid system (HNPs–DA) triggered by the low pH value of tumor microenvironment (pH 6.5) to enhance the uptake efficiency of NPs in cancer cells; the nanohybrid could exhibit T2-MR imaging enhancement and chemotherapy ability, ascribed to the loaded magnetite nanocluster (MNC) and paclitaxel (PTX), respectively. The HNPs–DA comprises two distinct functional components: (1) a biocompatible amphiphilic polymer (Pluronic F127) to act as a nanovehicle for MNC and PTX after self-assembly in an aqueous solution; and (2) a hydrophilic polymeric shell derived from stearoyl-polyethylenimine-2,3-dimethylmalefic anhydride (SC-g-PEI-DMMA). SC-g-PEI-DMMA switches the surface charge of the HNPs–DA from negative to positive by diminishing the anionic part of DMMA and sequentially recovering the cationic instinct of the PEI part at pH 6.5, which could facilitate the cellular uptake and therefore enhance the theranostic effects. In vitro studies demonstrated a darker T2-MRI image in the HNPs–DA-treated HepG2 cells at pH 6.5 as compared to that at pH 7.4. Moreover, CCK8 assay indicated that HNPs–DA exhibited a much higher cytotoxicity against HepG2 cells at pH 6.5, and flow cytometric analysis suggested that the cell death induced by HNPs–DA occurred via apoptosis, which was detected by Annexin V antibody and propidium iodide staining.
研究领域:
生物医学工程
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癌症治疗
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纳米医学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2010
·
IF 7.365
De-Hong Yu,Qin Lu,Jing Xie,Chao Fang,Hong-Zhuan Chen
Antiangiogenic cancer therapy can be achieved through the targeted delivery of antiangiogenic agents to the endothelial cells of tumor neovasculature. In the present study, we developed a drug delivery system (DDS), nanoparticles conjugated with K237-(HTMYYHHYQHHL) peptides for tumor neovasculature targeting drug delivery. Paclitaxel, a chemotherapeutic agent with potent antiangiogenic activity , was used as a prototype drug. We synthesized the aldehyde poly(ethylene glycol)–poly(lactide) (aldehyde-PEG–PLA) block copolymer by ring opening polymerization . The nanoparticles loading paclitaxel (PTX-NP) were fabricated using the O/W emulsion and evaporation technique. K237 ligand, a peptide that can bind to the KDR receptors predominantly expressed on the surface of tumor neovasculature endothelial cells with high affinity and specificity and inhibit the VEGF-KDR angiogenic signal pathway, was conjugated to the aldehyde group of PEG chain using the N-terminal PEGylation technique. The K237 conjugated paclitaxel-loaded nanoparticles (K237-PTX-NP) had a hydrodynamic diameter of 150 nm. The K237 density on nanoparticle surface was 474 and the mean distance between two neighboring PEG chains linked to K237 peptide was 12 nm. The K237 conjugated nanoparticles could be significantly internalized by human umbilical vein endothelial cells (HUVEC) through the K237-KDR interaction, and this facilitated uptake led to the expected enhanced antiangiogenic activity shown by HUVEC proliferation , migration and tube formation compared to cells treated with the commercial formulation Taxol ® and PTX-NP. The long-circulating property and the K237 ligand of K237-PTX-NP warranted rapid, long-term, and accurate in vivo tumor neovasculature targeting, and thereafter the significant apoptosis of tumor neovasculature endothelial cells and necrosis of tumor tissues of MDA-MB-231 breast tumors implanted in female BLAB/c nude mice . This nanoparticulate DDS offers a new strategy for paclitaxel chemotherapy application and it could also be used to carry other chemotherapeutic drugs, genes, and proteins with antiangiogenic activity for antiangiogenic cancer therapy.
研究领域:
药学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Luyao Yu,Yingxia Guo,Tonghe Liu,Yunlong Sheng,Meichen Liu,Ning Zhang,Jiye Tian,Chunpeng Feng,Meiyun Shi,Lei Yin
Paclitaxel (PTX) has poor aqueous solubility and vehicle-related toxicity. Polymeric micelles (PMs) can improve solubility and leverage the enhanced permeability and retention (EPR) effect for tumor targeting. However, a comprehensive understanding of their in vivo fate remains limited, due to the inability to distinguish between encapsulated and released drug. We developed a novel method integrating stable isotope tracing, ultrafiltration, and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to quantify free, released, and total PTX, the polymeric carriers methoxy-poly(ethylene glycol) (molecular weight ∼2,000 Da) (mPEG2K) and methoxy-poly(ethylene glycol)- block -poly(D,L-lactic acid) (mPEG block MW ∼2000 Da, PLA block MW ∼2,000 Da) (mPEG2K–PLA2K) in rats following administration of PTX injection and paclitaxel-loaded polymeric micelles (PTX-PMs). PTX-PMs significantly altered the pharmacokinetics, reducing the initial dose–normalized initial plasma concentration ( C 0 /Dose) of free PTX to 27.0% of that from the injection. Altered tissue distribution was observed, with high accumulation in reticuloendothelial system (RES) organs and more complete clearance by 48 h. Excretion studies revealed a substantially higher cumulative fecal excretion of PTX after PTX-PMs administration, while the polymer carrier was predominantly excreted renally as mPEG2K. These findings provide critical insights into the in vivo disposition of PTX nanoformulations, supporting the rational design of PMs-based delivery systems.
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Kaipei Luo,Shaoping Yin,Ruixia Zhang,Hua Yu,Guangji Wang,Juan Li
The efficient delivery of chemotherapeutic drugs to the tumor tissues unavoidably encounters numerous obstacles, such as poor tumor targeting capability, slow intracellular drug release and massive accumulation in the liver. In this study, by self-assembling methoxy poly (ethylene glycol)-poly (lactide) block copolymer (mPEG-PLA) and hyaluronic acid-paclitaxel conjugate (HA-PTX), the composite nanoparticles (mPPHP NPs) were fabricated for efficient therapy of cancer. mPPHP NPs formed self-assembled nanoparticles (116 nm in diameter) with a narrow size distribution; and showed a rapid release of PTX in the presence of hyaluronidase and esterase . mPPHP NPs exhibited enhanced internalization by cells via CD44 receptors and selected cytotoxicity against A549 cells in vitro . More importantly, compared with other PTX formulations, mPPHP NPs were demonstrated to present the reduced liver accumulation, excellent tumor-targeting ability and superior antitumor efficacy in vivo , with a TIR of 75.9%. The multifunctional composite nanoparticles could be developed as a promising nano-carrier for improved therapeutic efficacy.
研究领域:
肿瘤学
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纳米医学
·
药剂学
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分子靶向治疗
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药物递送系统
·
转化医学
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Heting Hou,Dong Zhang,Jiewen Lin,Yingying Zhang,Chengyong Li,Zhe Wang,Jiaoyan Ren,Maojin Yao,Ka-hing Wong,Yi Wang
Prodrug, in which the inactive parent drug with good bioavailability is metabolized into an active drug in the body, is one of the main strategies to target the disease site to improve the drug efficiency and reduce the adverse effects of chemotherapy. Because of the good capability of chemical modification, zein, a plant derived protein, and drugs can be conjugated through environmentally sensitive links to form prodrugs capable of triggered drug release. In this study, a novel prodrug was synthesized using paclitaxel (PTX), zein, and a disulfide linker, and nanoparticles were formed by self-assembly of the prodrug. An effective in vitro triggered release, 80–90% in 5 min, of the prodrug based nanoparticles (zein-S-S-PTX_NP) was successfully approached. The cytotoxicity of zein-S-S-PTX_NP as well as the zein encapsulation of PTX (zein_PTX_NP) and pure PTX on HeLa cells and NIH/3T3 fibroblast cells was tested using MTS assay. It showed that, after the treatment of zein-S-S-PTX_NP at the equivalent PTX concentrations of 0.1, 0.5, 1, and 5 μg/mL, respectively, zein-S-S-PTX_NP had zero damage to normal cells but a similar cytotoxicity to cancer cells as pure PTX. In the animal study, the tumor was 50% of the original size after the treatment of zein-S-S-PTX_NP for 9 days with 3 doses. This study suggested that the novel prodrug based nanoparticle zein-S-S-PTX_NP could be a promising approach in chemotherapy with targeted delivery, improved efficacy, and reduced side effects.
研究领域:
药物化学
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生物医学工程
·
肿瘤学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Ying Fang,KangRui Wang,Qin Li,ChengHong Huang
Carboxylation chitosan achieved by alkalization linked with ethyl vanillin to obtain Chitosan-ethyl vanillin (EV-CMCS) compound through Schiff base reaction and confirmed by FT-IR, UV, XRD, TG and NMR. EV-CMCS refluxed with GNRs for acquisition of EV-CMCS@GNRs nanocomposites for PTX Loading and release. Results demonstrated that both EV-CMCS and EV-CMCS@GNRs are nanoscale composites with excellent solubilization due to their micelle structure taking CMC values of 0.06683 mg/mL and 0.06537 mg/mL. It was found that the loading and encapsulation rate of EV-CMCS and EV-CMCS@GNRs for PTX are 19.59~37.64% and 60.36~80.79% as well as 20.99~37.02% and 58.78~79.77%. Compared with only the delayed release of EV-CMCS that it have 11.5% and 18.7% accumulative release amount for 24 h and 14.9% and 23.7% for 48 h under both pH 6.8 and 7.4, the EV-CMCS@GNRs represent sudden release that it have an accumulative release amount of 90.2% for 24 h and 96.0% for 48 h at pH 6.8. It deduced that the broken Schiff base under acidic condition can increase CMC of EV-CMCS@GNRs, which offered an alternative way for paclitaxel delivery for tumor therapy.
研究领域:
纳米技术
·
药学
·
材料科学
·
生物医学工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Zhichao Guan,Yue Chen,Wenjie Fan,Xiaoye Li,Yan Shi,Yujing He,Jifu Hao
A disulfide-bridged GA-ss-IND conjugate was synthesized, which spontaneously self-assembled into stable nanomicelles. • Molecular dynamics simulations revealed that hydrophobic and van der Waals interactions dominate GA-ss-IND self-assembly. • The fabricated nanomicelles exhibited prominent GA receptor-mediated liver targeting and GSH-stimuli-responsive release. Conventional paclitaxel (PTX) chemotherapy for hepatocellular carcinoma (HCC) is severely restricted by insufficient tumor-targeting specificity, unsatisfactory therapeutic efficacy, and marked systemic toxicity. To address these drawbacks, a redox-responsive and liver-targeted nanoplatform was designed for efficient PTX delivery in HCC therapy. Herein, we synthesized a disulfide-bridged amphiphilic glycyrrhetinic acid-indomethacin prodrug conjugate (GA-ss-IND), which could spontaneously self-assemble into uniform nanomicelles driven by hydrophobic interaction and van der Waals forces, as verified by molecular dynamics simulations. After PTX encapsulation, the fabricated PTX@GA-ss-IND nanomicelles (NMs) displayed regular spherical morphology and favorable colloidal stability. In vitro drug release experiments showed that the nanomicelles displayed prominent redox-responsive release behavior, achieving rapid and on-demand PTX release in high-glutathione intracellular tumor microenvironments. Benefiting from the glycyrrhetinic acid-mediated receptor targeting, cellular uptake assays and ex vivo organ imaging results demonstrated the prominent liver-targeting accumulation of PTX@GA-ss-IND NMs. In vitro cytotoxicity evaluation revealed that the fabricated nanosystem exhibited better antiproliferative activity against HepG2 cells compared with free PTX. Moreover, this nanoplatform effectively improved the in vivo bioavailability of PTX and reduced systemic adverse effecs. In conclusion, the constructed redox-responsive and liver-targeted nanodelivery system presents a feasible and promising strategy for precise and safe chemotherapy toward hepatocellular carcinoma. Download: Download high-res image (182KB) Download: Download full-size image
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DOI
高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Yixing Li,Zhongjun Pan,Chen Ling,Jiahao Yuan,Shasha Li,Ruijiang Liu
α-Fe 2 O 3 /Fe 3 O 4 MHNTs were prepared by the hydrothermal and calcination-reduction method. • A targeted paclitaxel delivery nanosystem based on α-Fe 2 O 3 /Fe 3 O 4 MHNTs was fabricated for its antitumor activity against A549 cells. • The delivery nanosystem exhibited excellent biocompatibility, pH responsiveness, sustained-release properties, and antitumor effects. • In vitro studies demonstrated that the cytotoxic effect on A549 cells was mainly mediated via the apoptosis pathways, accompanied by the involvement of ferroptosis. Paclitaxel (PTX), a first-line chemotherapeutic agent, suffers from poor tumor targeting and off-site toxicity, which can easily cause damage to the hematopoietic, digestive, and nervous systems. Magnetic targeting delivery strategies offer a promising solution to address this challenge. Herein, we innovatively prepared α-Fe 2 O 3 /Fe 3 O 4 magnetic heterogeneous nanotube (MHNTs) via a hydrothermal and calcination-reduction method. After being modified with PEG 2000 and loaded with PTX, α-Fe 2 O 3 /Fe 3 O 4 -PEG-PTX delivery nanosystem exhibited both good biocompatibility and pH responsiveness, with an average length and average wall thickness of 174 nm and 37.9 nm, respectively. The encapsulation efficiency and drug loading efficiency of paclitaxel in the α-Fe 2 O 3 /Fe 3 O 4 -PEG-PTX nanocomposites reached 98.4% and 37.4%, individually. In vitro studies demonstrated that this nanosystem exhibited excellent magnetic responsiveness. Under the influence of a magnetic field, the viability of A549 cells decreased to 33% after 72 h of coincubation with the nanocomposite, accompanied by elevated intracellular peroxidation levels and ROS content. Further Western blot analysis of related proteins revealed that the nanocomposite induced A549 cell death via activation of the caspase-dependent apoptosis pathway, accompanied by the involvement of ferroptosis. The drug release process of this magnetic delivery nanosystem was stable and controllable, providing a promising strategy for enhancing the delivery efficiency of insoluble drugs and improving the therapeutic efficacy for lung cancer. A targeted paclitaxel delivery nanosystem based on α-Fe 2 O 3 /Fe 3 O 4 MHNTs fabricated via the hydrothermal and calcination-reduction process was constructed for antitumor. This targeted paclitaxel nanosystem exerted its cytotoxic effect on A549 human lung cancer cells by inducing apoptosis, with ferroptosis also involved in the process, confirming its potential for clinical translation in lung cancer treatment. Download: Download high-res image (129KB) Download: Download full-size image
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DOI
PubMed
高影响因子
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
·
2026
·
IF 2.7
Xinyue Zhang,Weiwei Xie,Yuqian Zhang,Ye Yuan,Jingpu Xu,Jian Liu
IntroductionNab-paclitaxel is a mainstay of treatment for a broad spectrum of cancers and is typically administered over multiple cycles. The anti-mitotic effects of nab-paclitaxel are well-established. However, the systemic impact of consecutive treatment cycles on host physiology remains largely unexplored. Of particular interest is the gut microbiota and its regulatory role in drug metabolism. This study aimed to investigate the effects of consecutive nab-paclitaxel chemotherapy cycles on gut microbiota composition, intestinal barrier function, and pharmacokinetic (PK) behavior in rats.MethodsTwenty-four Sprague–Dawley rats were randomly assigned to one-, two-, or three-cycle chemotherapy groups and received nab-paclitaxel via tail vein injection. Plasma drug concentrations were measured by Liquid Chromatography–Tandem Mass Spectrometry (LC–MS/MS), gut microbial composition was analyzed using 16S Ribosomal RNA (16S rRNA) sequencing, and hepatic CYP3A and CYP2C expression was assessed by Western blot and Quantitative Polymerase Chain Reaction (qPCR).ResultsConsecutive nab-paclitaxel administration significantly altered the gut microbiota, decreasing Actinobacteriota and Firmicutes while increasing Proteobacteria and Cyanobacteria in a cycle-dependent manner. Microbial diversity indices, including Observed species and Rao's quadratic entropy, increased after multiple cycles. Pharmacokinetic analysis showed that clearance, mean residence time, and volume of distribution decreased, whereas Area Under the Curve (AUC) and Maximum Plasma Concentration (Cmax) increased significantly after repeated dosing. However, no significant differences were observed in CYP3A1 or CYP2C11 protein or Messenger RNA (mRNA) expression, suggesting that nab-paclitaxel may influence pharmacokinetics through non-CYP–dependent pathways potentially mediated by gut microbiota–host interactions.ConclusionIn conclusion, consecutive nab-paclitaxel chemotherapy cycles induce gut microbiota dysbiosis and alter pharmacokinetic profiles via non-CYP–dependent mechanisms, highlighting the critical role of the microbiota–gut–liver axis in chemotherapeutic drug disposition and providing a theoretical basis for microbiota-targeted interventions to optimize chemotherapy efficacy.
✓ 已验证
DOI
PubMed
高影响因子
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