DRUG DELIVERY
·
2019
·
IF 3.829
Xiaorong Zhou,Chuanpei Cao,Nan Li,Shaofei Yuan
The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on β-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (β-elemene and PTX), tumor targeting ligand (3’-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. β-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of β-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2016
·
IF 3.975
Shuxin Xu,Hongxia Fan,Li Yin,Jianhua Zhang,Anjie Dong,Liandong Deng,Hua Tang
Intraperitoneal (IP) chemotherapy is a preferable treatment option for peritoneal carcinomatosis of malignancies by delivering chemotherapeutic drugs into the abdominal cavity. A persistent major challenge in IP chemotherapy is the need to provide effective drug concentration in the peritoneal cavity for an extended period of time. In the present work, the thermosensitive hydrogel system (PTX/PECT gel ) assembled by PTX (paclitaxel)-loaded amphiphilic copolymer (PECT, poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly (ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)) nanoparticles was developed for sustained IP chemotherapy of peritoneal carcinomatosis model. Cytotoxicity assay indicated that PECT hydrogel was biocompatible with very low cytotoxicity and PTX/PECT gel had enhanced cytotoxicity than free PTX. In vivo toxicity study demonstrated the biocompatibility and biosafety of PECT hydrogel as an IP chemotherapy carrier. The fluorescence imaging method was employed to monitor the intraperitoneal degradation of PECT hydrogel by labeling PECT with rhodamine B. PECT hydrogel with the dose of 200 μL showed about 8 days’ retention time and most of the injected hydrogel was located in the intestine. The anti-tumor efficacy study was carried out in mice bearing CT26 intraperitoneal ascites fluid as colorectal peritoneal carcinomatosis model. The result showed that intraperitoneal administration of PTX/PECT gel could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo , compared with Taxol® group. The pharmacokinetic studies demonstrated that PTX/PECT gel could improve the bioavailability of PTX by being formulated in PECT hydrogel. Overall, sustained drug concentration at peritoneal levels in combination with drug in the form of nanoparticle contributes to the enhanced anti-tumor efficacy. Thus, our results suggested that PTX/PECT gel may have great potential applications in IP chemotherapy.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Qianqian Qi,Zhanyu Zhang,Dun Wang
The lack of targeting and poor solubility of anti-tumor drugs are two major limitations to the outcome of tumor therapy. To address the inherent drawbacks, we designed a novel prodrug of paclitaxel (PTX), HP-PTX. This HP-PTX prodrug contains a PEGylated heptamethylene cyanine dye (PEG-IR808–1) that was conjugated to PTX via a redox-sensitive disulfide bond. The moiety of IR808–1 acts as a tumor-targeting ligand, enabling HP-PTX not only to target tumor cells, but also to localize to mitochondria and generate ROS under 808 nm laser irradiation to wound cellular mitochondria thus exerting cytotoxic effect. Meanwhile, in vitro cellular uptake assays showed that HP-PTX possesses MCF-7 cell tumor targeting specificity which was attributed to the preferential uptake of heptamethine cyanine dye mediated by the overexpressed organic anion-transporting polypeptides (OATP) on MCF-7 cell membrane. Near-infrared in vivo imaging showed that incorporation of polyethylene glycol effectively prolonged prodrug's half-life in vivo. In addition, in vivo experiments showed that with combinational therapy strategy HP-PTX was able to kill cancer cells with high efficiency (69.52 %) without notable toxic side effects compared to PTX. These results are evidence of the potential of the tumor-targeting prodrug HP-PTX for the treatment of breast cancer.
研究领域:
肿瘤学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Huifang Yao,Xiaobo Xiong,Feng Wu,Xiangyang Hu
The general mechanism of chemotherapeutic resistance is related to changes in the uptake and efflux rate of chemotherapeutic drugs or intracellular transport. In the progress of photodynamic and PTX combination therapy, the excessive use of photosensitizers (PSs) may cause side effects. Since PSs are exposed to light, they can still cause ongoing damage to normal cells. To effectively reduce this side effect, we propose a strategy to regulate the concentration of PTX in resistant cells using low concentrations of AIEgen PSs. In this work, the molecular structure of four AIEgen PSs ( TPEPy , TPECPy , TPAPy , and TPESPy ) were designed and synthesized featuring different “D−π−A” type structures. They displayed excellent optical properties , good biocompatibility , good PDT effect, mitochondrial targeting and cell imaging . Among these AIEgen PSs, TPESPy exhibited the strongest PDT effect in tumor cells and PTX resistant tumor cells. The reversal coefficient of PTX resistant tumor cells can be achieved as 2214. In addition, to demonstrate the transport mechanism of PTX within tumor cells, we further study the effect of uptake and expel PTX in the PTX resistant SKOV-3 cells. The results show the rate of uptake and expel PTX for PTX resistant SKOV-3 cells can be effectively changed by controlling the concentration of AIEgen PSs and light irradiation time, providing precise treatment options for drug-resistant tumor cells.
研究领域:
生物化学
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Fang Wang,Jian Yuan,Qian Zhang,Siqian Yang,Shaohua Jiang,Chaobo Huang
Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are an ideal paclitaxel (PTX)-carrying system due to its biocompatibility and biodegradability. But it possessed disadvantage of drug burst release. In this research, a layer-by-layer deposition of chitosan (CS) and sodium alginate (ALG) was applied to modify the PLGA nanoparticles. The surface charges and morphology of the PLGA, PLGA/CS and PLGA/CS/ALG particles was measured by capillary electrophoresis and SEM and TEM, respectively. The drug encapsulation and loading efficiency were confirmed by ultraviolet spectrophotometer. The nanoparticles were stable and exhibited controlled drug release performance, with good cytotoxicity to human lung carcinoma cells (HepG 2). Cumulatively, our research suggests that this kind of three-layer nanoparticle with LbL-coated shield has great properties to act as a novel drug-loaded system.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Hong Shen,Changwei Zhang,Chengzhang Wang,Jianxin Jiang,Fengxia Tang,Chuan Li,Hua Yuan,Xiaoran Yang,Zhenkai Tong,Yi Huang
Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity release of liposomes may severely limit their further applications. In this study, based on the characteristics of lutein (L) photo-response and orthoester (OE) acid-response, stable and dual-responsive liposomes (Dr-lips) have been prepared. The Dr-lips exhibited a spherical shape with a uniform size of approximately 58.27 nm. Moreover, they displayed a zeta potential ranging from −45.45 to −28.25 mV and showed excellent storage stability, indicating stable colloidal properties. Additionally, they achieved high drug encapsulation rates, with 92.27% for PTX and 90.34% for Ce6, respectively. Meanwhile, under near-infrared (NIR) light at 660 nm, Ce6 plays a key role in accelerating the photodegradation rate of lutein and PEG-OE-L while also enhancing tissue penetration ability. Additionally, Dr-lips loaded with Ce6 and PTX not only displayed excellent pH and photo dual-responsiveness for targeted delivering and releasing but also showed remarkable reactive oxygen species (ROS) generation capacity and impressive anti-tumor activity in vitro. Therefore, it provides a novel strategy for optimizing stability and enhancing their targeted drug delivery of liposome.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Hang Gao,Hang Li,Shuaiqiang Shao,Lintongqing Tan,Yudie Wang,Dawei Li,Wen Zhang,Tao Zhu,Guangchun Liu,Xin Meng
Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.
研究领域:
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2023
·
IF 3.9
Fang Chen,Li Yin,Teng He,Tao Chen,Hangbo Yue,Chufen Yang
To enhance the stability of the polymeric micelles and optimize their drug-controlled release ability, three disulfide-linked polyethylene glycol methyl ether methacrylate–disulfide–poly(ε-caprolactone-co-γ-amine−ε-caprolactone) (PPEGMA-SS-P(CL-co-ACL)) polymers were synthesized and characterized by 1H NMR, GPC, and FT-IR successfully, and their dual pH/reduction-responsive cross-linked polymeric micelles were prepared for paclitaxel (PTX) delivery by using 2,3-dimethylmaleic anhydride (DMMA) as the cross-linking agent. The PTX loading capacity (LC) and encapsulation efficiency (EE) values of the cross-linked micelles formed by PPEGMA8-SS-P(CL47-co-ACL15) achieved were 23.96% and 71.58%, slightly higher than those of un-cross-linked micelles. Both particle sizes of blank micelles and in vitro drug release of PTX-loaded micelles confirmed that compared with those un-cross-linked micelles, the cross-linked micelles were more stable at pH 7.4 + 0 mM DTT, with a PTX cumulative release of 13% at 120 h, while the PTX cumulative release of the cross-linked micelles at pH 5.0 + 10 mM DTT were close to that of un-cross-linked micelles after 60 h, indicating the successful reversible cross-linking and smooth drug release of the cross-linked micelles. The cytotoxicity assay showed that PPEGMA8-SS-P(CL47-co-ACL15) and its cross-linked micelles had low cell cytotoxicity, and both PTX-loaded micelles revealed a certain inhibitory effect on HepG2 cells. These results revealed that the dual pH/reduction-responsive cross-linked polymeric micelles prepared from PPEGMA8-SS-P(CL47-co-DCL15) were a promising candidate for PTX delivery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2022
·
IF 3.461
Chunyan Yang,Zhongzhen Yang,Siqi Wang,Jinxia Chen,Qijun Liu,Tianle Huang,Li Hai,Runxin Lu,Yong Wu
Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood–brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells. BBR, due to its delocalized positive electricity and lipophilicity, can be attracted by mitochondrial membrane potential and concentrate on mitochondria to achieve mitochondrial targeting and induce cell apoptosis. By simultaneously modifying the liposome with FA and BBR to deliver drugs, leads to a good therapeutic effect of glioma through FA-based glioma targeting and BBR-based mitochondrial targeting. In addition, the surface of the liposome was coated with Tween 80 to further improve BBB penetration. All results exhibited that PTX-Tween 80-BBR + FA-Lip can observably improve the chemotherapy therapeutic efficacy through the highly specific tumor targeting and mitochondrial targeting, which can provide new ideas and methods for the targeted therapy of glioma.
研究领域:
药学
·
神经肿瘤学
·
药物递送系统
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Research Express
·
2021
·Vol. 8
·期 4
·045012
·
IF 1.62
Fei Ge,Rui Qiao,Ping Song,Yugui Tao,Longbao Zhu,Weiwei Zhang,Wanzhen Li,Lin Gui
Tumors area common cause of morbidity and mortality. High treatment efficiency and low drug toxicity are key for effective tumor treatment. Here, the pH-sensitive material ZIF-90 was synthesized by the liquid-phase diffusion method for loading paclitaxel (PTX), and the targeting peptide (RGD) was prepared by the solid-phase synthesis method to modify it (RGD/PTX@ZIF-90). The skeleton of RGD/PTX@ZIF-90 collapses in the acidic tumor microenvironment, thereby releasing PTX and mediating the controlled release of the drug. ZIF-90 below 300 nm was obtained by adjusting the ratio of metal ions and organic ligands in the characterization experiment. In addition, in vitro drug release experiments showed that the drug release rate was greater at pH = 5.5 than at pH = 7.4. The lethal rate of RGD/PTX@ZIF-90 to human breast cancer cells (MCF-7) was 44.5%, which was higher than the lethal rate of PTX alone (37.3%) in the cytotoxicity experiment and apoptosis experiment. Uptake experiments revealed that RGD/PTX@ZIF-90 mainly existed in the cytoplasm of MCF-7, which suggests that the drug had successfully entered the cell to achieve the therapeutic effect. The loading of the nano-medicine carrier ZIF-90 and the modification of the targeting peptide RGD significantly improve the therapeutic effect of PTX and indicate that this system could be used to treat breast cancer.
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
高影响因子
Results in Engineering
·
2026
·
IF 9.4
Saichao Wei,Haitao Zhang,Zhou Fang,Jiawang Shi,Baoying Li,Zhenjing Liu,Yahui Song,Jiaqi Xu,Qian Yu,Min Zhang,Kehai Liu
Engineering a combination chemotherapy of PTX and copper complex has advantages. PTX treatment of tumor cells can increaseH 2 O 2 , providing a substrate for copper to trigger the decomposition of H 2 O 2 through a Fenton-like reaction and to generate ROS, thereby causing DNA damage in tumor cells. However, due to the short half-life and limited diffusion distance of ROS, the anti-tumor efficacy is reduced. This problem can be overcome by delivering copper into the nucleus to achieve in situ Fenton-like reaction induction and ROS release therein. Here, we fabricated a hierarchical delivery system where PTX was connected to polyethyleneimine by disulfide bond, and then modified with a nuclear localization signal peptide. Finally, copper loading was realized by the rich amine-mediated coordination of PEI, and the Cu/PSPN nanoplatform was obtained. The results showed that Cu/PSPN exhibited an appropriate particle size (245 nm) and zeta potential (+1.88 mV), with minimal hemolytic toxicity. Cu/PSPN achieved hierarchical transport of PTX and copper in the cytoplasm and nucleus through glutathione responsiveness and NLS-mediated delivery. Cu/PSPN induced an efficient Fenton-like reaction in the nucleus, significantly enhancing the anti-tumor efficacy of PTX by increasing ROS generation and apoptosis rates to 1.82-fold and 3.89-fold those of the PTX group, respectively. Cu/PSPN also demonstrated superior anti-tumor efficacy in vivo with tumor weight and volume being approximately 6.8% and 10.5% of the free PTX group. This study provides a robust engineering strategy for significantly improving the anti-tumor efficacy of PTX based on the in situ generation of ROS in the nucleus.
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产品关联
DOI
高影响因子
Small
·
2024
·
IF 13
Sipin Zhu,Qiuji Wu,Yibo Ying,Yuqin Mao,Wenjie Lu,Jie Xu,Xiong Cai,Huacheng He,Jiang Wu
Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties. The hydrogel is used to deliver paclitaxel (PTX) together with basic fibroblast growth factor (bFGF) to inhibit glial scar formation as well as promote axon regeneration and motor function for SCI repair. Due to the specific interaction of BSA with both drugs, bFGF, and PTX can be controllably released from the hydrogel system to achieve an effective concentration at the wound site during the SCI regeneration process. Moreover, benefiting from the combination of PTX and bFGF, this bFGF/PTX@BSA system significantly aided axon repair by promoting the elongation of axons across the glial scar with reduced reactive astrocyte secretion. In addition, remarkable anti-apoptosis of nerve cells is evident with the bFGF/PTX@BSA system. Subsequently, this multi-functionalized drug system significantly improved the motor function of the rats after SCI. These results reveal that bFGF/PTX@BSA is an ideal functionalized material for nerve repair in SCI.
研究领域:
神经科学
·
生物医学工程
·
药学
✓ 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）