BIOMATERIALS
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2015
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IF 8.557
Tingjie Yin,Lei Wang,Lifang Yin,Jianping Zhou,Meirong Huo
In this study, a novel redox-sensitive micellar system constructed from a hyaluronic acid-based amphiphilic conjugate (HA-ss-(OA-g-bPEI), HSOP) was successfully developed for tumor-targeted co-delivery of paclitaxel (PTX) and AURKA specific siRNA (si-AURKA). HSOP exhibited excellent loading capacities for both PTX and siRNA with adjustable dosing ratios and desirable redox-sensitivity independently verified by morphological changes of micelles alongside in vitro release of both drugs in different reducing environments. Moreover, flow cytometry and confocal microscopy analysis confirmed that HSOP micelles were capable of simultaneously delivering PTX and siRNA into MDA-MB-231 breast cancer cells via HA-receptor mediated endocytosis followed by rapid transport of cargoes into the cytosol. Successful delivery and transport amplified the synergistic effects between the drugs while leading to substantially greater antitumor efficacy when compared with single drug-loaded micelles and non-sensitive co-loaded micelles. In vivo investigation demonstrated that HSOP micelles could effectively accumulate in tumor sites and possessed the greatest antitumor efficacy over non-sensitive co-delivery control and redox-sensitive single-drug controls. These findings indicated that redox-sensitive HSOP co-delivery system holds great promise for combined drug/gene treatment for targeted cancer therapy.
研究领域:
药剂学
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肿瘤学
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PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2016
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IF 3.42
Yang Qiu,Chao Wu,Jie Jiang,Yanna Hao,Ying Zhao,Jie Xu,Tong Yu,Peng Ji
A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination.
研究领域:
药剂学
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生物医学工程
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肿瘤学
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Xiaoye Yang,Xiaoqun Shi,Yanan Zhang,Jiangkang Xu,Jianbo Ji,Lei Ye,Fan Yi,Guangxi Zhai
To improve the anti-cancer therapeutic effect of nanosystems for chemo-photodynamic therapy, there remain several hurdles to be addressed, e.g. , limited co-loading efficiency, insufficient stimulus-responsiveness and lack of synergetic effect. This work reported novel reactive‑oxygen-species (ROS)-responsive chlorin e6 (Ce6) and paclitaxel (PTX) co -encapsulated chondroitin sulfate- g -poly (propylene sulfide) nanoparticles (CP/ChS- g -PPS NPs), wherein the drug loading efficiencies of Ce6 and PTX were as high as 14.93% and 24.31%, respectively. To enlarge the ROS signal at tumor sites thus enhancing the ROS-responsiveness of ChS- g -PPS NPs, near-infrared (NIR) light was utilized to induce Ce6 to produce more ROS to destruct the NPs. Our data showed that the photo-triggered self-destructive property of NPs helped drugs to spread deeper in tumors upon laser irradiation, making the NPs promising to thoroughly remove tumor cells. CP/ChS- g -PPS NPs exhibited a synergetic chemo-photodynamic therapy effect in vitro , which was suggested by the combination indexes of PTX and Ce6 lower than 1 when 20–80% inhibition rates of MCF-7 cells were achieved. As for the in vivo antitumor activity , the tumor inhibition rates of CP/ChS- g -PPS NPs (with laser irradiation) were as high as 92.76% and 88.57% in 4T1 bearing BALB/c mice and MCF-7 bearing BALB/c nude mice, respectively, which were significantly higher than those of other treatment groups. This work provided a simple yet effective strategy to develop photo-triggered ROS-responsive NPs for synergetic chemo-photodynamic therapy with quick ROS-responsive self-destruction, spatiotemporally controllability, reduced off-target toxicity, and desirable therapeutic effect.
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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生物医学工程
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高影响因子
PHARMACEUTICAL RESEARCH
·
2015
·Vol. 32
·期 8
·2649-2662
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IF 3.42
Gao Yajie,Zhang Chao,Zhou Yanxia,Li Jinwen,Zhao Lei,Li Yushu,Liu Yan,Li Xinru
Purpose The purpose of the present study was to design and fabricate endosomal pH-sensitive dual-ligand-modified micellar nanoparticles to achieve enhanced drug delivery to tumor cells and facilitated intracellular drug release. Methods End-group-carboxylated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) and cyclic Arg-Gly-Asp-Tyr-Lys- and anti-prostate specific membrane antigen antibody-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) were synthesized and characterized by 1 H NMR and gel permeation chromatography, and self-assembled into micelles. Paclitaxel-loaded dual-ligand-modified micelles were prepared by thin-film hydration method, and characterized by dynamic light scattering, transmission electron microscope, pH-dependent in vitro release and stability. Intracellular paclitaxel delivery was measured by flow cytometry and imaged by confocal microscopy. In vitro cytotoxicity was studied in the 22Rv1 xenograft prostate tumor cell lines. Results The prepared dual-ligand-modified micelles with about 30 nm in diameter and rapid intracellular drug release behavior at endo/lysosomal pH were very effective in enhancing the cytotoxicity of paclitaxel against 22Rv1 cells by increasing the cellular uptake, which was verified the correlation with the expression of integrin α v β 3 and prostate specific membrane antigen in tumor cells by flow cytometric analysis and confocal microscopy, compared with single ligand-modified micelles. Conclusion These findings provided valuable information that the application of combining of dual-ligand modifications with pH-sensitivity to polymeric micelles may be a promising approach in the efficient delivery of anticancer drugs for treatment of integrin α v β 3 and prostate specific membrane antigen expressing prostate cancers.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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纳米技术
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International Journal of Nanomedicine
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2023
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IF 8
Qiang Huo,Jianhua Zhu,Yimin Niu,Huihui Shi,Yaxiang Gong,Yang Li,Huihui Song,Yang Liu
Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glyco-protein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l-lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy.
研究领域:
药剂学
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纳米技术
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肿瘤学
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药物递送系统
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PubMed
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Wenyou Fang,Mingchao Xu,Huiru Li,Lujun Wang,Wenjie Lu,Xia Liu,Shengqi Chen,Song Gao,Qing Zhang,Rongfeng Hu
In colorectal cancer, the cancer-immunity cycle is often disrupted by the lack of effective tumor-associated antigens, impaired activation of antigen-presenting cells, and insufficient T cell infiltration, leading to tumor immune escape and disease progression. Therefore, we developed PTX-GLSO SEDDS@GLS (PGS@GLS), a multicomponent solid self-emulsifying drug delivery system (SEDDS) incorporating paclitaxel (PTX) and Ganoderma lucidum spore oil (GLSO), with processed Ganoderma lucidum spores (GLS) as the solid carrier. The intestinal lymphatic absorption of PTX-GLSO SEDDS was significantly enhanced after GLS solidification, facilitating the induction of immune responses. Additionally, the oil phase of GLSO enhanced PTX solubility through self-emulsification into nanoemulsion. In tumors and the mesenteric lymphatic system, PGS@GLS induced robust immunogenic cell death and triggered the release of damage-associated molecular patterns, thereby initiating the cancer-immunity cycle. Furthermore, GLSO and GLS synergistically promoted dendritic cell maturation and cytotoxic T cell activation, thereby potentiating anti-tumor immune responses. Tumor cells were killed by the accumulated cytotoxic T cells, and the resulting dead tumor cells released additional tumor-associated antigens, which were subsequently presented by dendritic cells, creating a positive feedback loop to amplify the cancer-immunity cycle. Notably, PGS@GLS maintained potent antitumor efficacy while mitigated PTX-related systemic toxicity, representing a promising oral chemoimmunotherapy platform that restores antitumor immunity through lymphatic transport-mediated cancer-immunity cycle reinforcement.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2020
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IF 5.573
Xin Deng,Ruiyao Mai,Chenyu Zhang,Dianbao Yu,Yichang Ren,Gang Li,Binbin Cheng,Ling Li,Zhiqiang Yu,Jianjun Chen
To ameliorate the deficiencies (e.g. solubility, membrane permeability and non-selective cytotoxicity) of paclitaxel (PTX), we synthesized a “smart” PDC (peptide-drug conjugate), by linking PTX with a multifunctional peptide consisting of a tumor targeting peptide (TTP) and a cell penetrating peptide (CPP), to construct the TTP-CPP-PTX conjugate , LTP-1. LTP-1 could intelligently deliver PTX into LHRH receptor-overexpressed MCF-7 cells, showing 2 times higher cellular uptake than PTX, and enhanced cytotoxicity with IC 50 of 3.8 nM (vs 6.6 nM for PTX). LTP-1 exhibited less cytotoxicity to normal cells and the ability to overcome PTX-resistance. Furthermore, LTP-1 had higher in vivo antitumor efficacy than PTX (TGI of 83.4% and 65.7% for LTP-1 and PTX, respectively, at 12 mmol/kg) without apparent toxicities. In summary, we proposed and testified the concept of constructing a novel PDC molecule, which can potentially conquer the drawbacks of PTX. LTP-1 represents a new class of antitumor PDC deserving further investigation.
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高影响因子
IET Nanobiotechnology
·
2023
·Vol. 17
·期 5
·406-419
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IF 2.3
Changhai Wang,Yuwen Jiao,Xinyu Zhang,Mingxue Guo,Qing Zhang,Wenjun Hu,Shuang Dong,Tangthianchaichana Jakkree,Yang Lu,Jinling Wang
As a first-line anticancer drug, paclitaxel has shortcomings, such as poor solubility and lack of tumour cell selectivity, which limit its further applications in clinical practice. Therefore, the authors aimed to utilise the characteristics of prodrug and nanotechnology to prepare a reactive oxygen species (ROS) and GSH dual-responsive targeted tumour prodrug nanoparticle Man-PEG-SS-PLGA/ProPTX to improve the clinical application status of paclitaxel limitation. The characterisation of Man-PEG-SS-PLGA/ProPTX was carried out through preparation. The cytotoxicity of nanoparticles on tumour cells and the effect on apoptosis of tumour cells were investigated by cytotoxicity assay and flow cytometry analysis. The ROS responsiveness of nanoparticles was investigated by detecting the ROS level of tumour cells. The tumour cell selectivity of the nanoparticles was further investigated by receptor affinity assay and cell uptake assay. The particle size of Man-PEG-SS-PLGA/ProPTX was (132.90 ± 1.81) nm, the dispersion coefficient Polymer dispersity index was 0.13 ± 0.03, and the Zeta potential was (−8.65 ± 0.50) mV. The encapsulation rate was 95.46 ± 2.31% and the drug load was 13.65 ± 2.31%. The nanoparticles could significantly inhibit the proliferation and promote apoptosis of MCF-7, HepG2, and MDA-MB-231 tumour cells. It has good ROS response characteristics and targeting. The targeted uptake mechanism is energy-dependent and endocytosis is mediated by non-clathrin, non-caveolin, lipid raft/caveolin, and cyclooxygenase (COX)/caveolin with a certain concentration dependence and time dependence. Man-PEG-SS-PLGA/ProPTX is a tumour microenvironment-responsive nanoparticle that can actively target tumour cells. It restricts the release of PTX in normal tissues, enhances its selectivity to tumour cells, and has significant antitumour activity, which is expected to solve the current limitations of PTX use.
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高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 16
·2667-2677
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IF 5.047
Meiyan Liu,Pingsheng Huang,Weiwei Wang,Zujian Feng,Jianhua Zhang,Liandong Deng,Anjie Dong
The precise locoregional co-delivery of multi-agents is an attractive strategy for combination cancer therapy, with the imperative requirement of an ideal injectable hydrogel platform with immense adaptability and multicomponent compatibility to achieve synergetic therapeutic efficiency. Herein, the methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (mPECT) diblock copolymer was empolyed to prepare mPECT-modified gold nanorods (AuNR-PECT) and paclitaxel-loaded mPECT nanoparticles (PTX/mPECT NPs). Then, an injectable nanocomposite hydrogel (AuNR/PTXmPECTgel) was fabricated by the host–guest inclusion between AuNR-PECT, PTX/mPECT NPs and α-cyclodextrin. A single local injection of AuNR/PTXmPECTgel could deposit abundant PTX/mPECT NPs (20% w/w) and AuNRs at the target location, which then sustainedly released PTX/mPECT NPs at a constant rate for two weeks and exhibited outstanding photothermal effects by near-infrared radiation. As a result, complete tumor regression after peritumoral injection of AuNR/PTXmPECTgel and effective inhibition of tumor recurrence after injection of AuNR/PTXmPECTgel in the postoperative cavity were observed in breast cancer mouse models; this can be attributed to the in situ synergetic chemo-photothermal anticancer efficiencies of AuNR and the PTX/mPECT NPs. Remarkably, this injectable hydrogel platform constructed by supramolecular assembly of multi-nanoagents can be facilely extended to local combination therapies of different therapeutic agents.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
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IF 1.911
Shiya Zhou,Wei Sun,Yinglei Zhai
Currently, nanoparticles (NPs) made of amphiphilic block copolymer are still an essential part of drug delivery system. Here, we report a novel amphiphilic block copolymer and paclitaxel (PTX)-loaded copolymer NPs for the controlled delivery of PTX. The block copolymer was synthesized via melt polycondensation method of methoxy poly(ethylene glycol) (mPEG), sebacic acid (SA) and ricinoleic acid (RA). A series of characterization approaches such as Fourier Transform Infrared Spectroscopy (FTIR), 1Hydrogen-Nuclear Magnetic Resonance (1H-NMR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD) and Gel Permeation Chromatography (GPC) applied have shown that the amphiphilic block copolymer was prepared as designed. NPs prepared by nanoprecipitation method consist of mPEG segments as the hydrophilic shell and RA-SA segments as the hydrophobic core, hydrophobic PTX was encapsulated as model drug. Subsequently, Transmission Electron Microscopy (TEM) analysis indicated that the spherical NPs have effective mean diameters ranging from 100 to 400 nm. Dynamic Light Scattering (DLS) analysis also revealed the controllable NPs diameter by modulating the mass ratio of RA to SA and drug loading amount (DLA). Besides, biphasic profile with zero order drug release was observed in general in vitro release behaviors of PTX from NPs. Further investigation confirmed that the release behaviors depend on the crystallinity of hydrophobic RA-SA segments. Results above suggest that NPs with amphiphlic block copolymer mPEG-b-P(RA-SA)-b-mPEG have a remarkable potential as a carrier for hydrophobic drug delivery in cancer therapy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Chunlai Feng,Haisheng Zhang,Jiaming Chen,Siqi Wang,Yuanrong Xin,Yang Qu,Qi Zhang,Wei Ji,Fumiyoshi Yamashita,Mengjie Rui,Ximing Xu
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro , combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization. The obtained co-loaded lipodisks were approximately 30 nm with a pH-sensitive property. The ratiometric co-delivery of two drugs via lipodisks was confirmed in both the drug-resistant MCF-7/ADR cell line and its parental MCF-7 cell line in vitro , as well as in a tumor-bearing mouse model in vivo compared with a cocktail solution of free drugs. Co-loaded lipodisks exerted improved cytotoxicity to tumor cells in culture, particularly to drug-resistant tumor cells at synergistic drug ratios. In an in vivo xenograft mouse model, the anti-tumor ability of co-loaded lipodisks was evidenced by the remarkable inhibitory effect on tumor growth of either MCF-7 or MCF-7/ADR tumors, which may be attributed to the increased and ratiometric accumulation of both drugs in the tumor tissues. Therefore, tumor-specific lipodisks were crucial for the combination treatment of DOX and PTX to completely exert a synergistic anti-cancer effect. It is concluded that for co-loaded lipodisks, cytotoxicity data in vitro could be used to predict their inhibitory activity in vivo , potentially enhancing the clinical outcome of synergistic therapy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Jiahao Lin,Qiang Cai,Yinian Tang,Yanjun Xu,Qian Wang,Tingting Li,Huihao Xu,Shuaiyu Wang,Kai Fan,Zhongjie Liu,Yipeng Jin,Degui Lin
Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754 nm and particle size of 115 ± 15 nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10–15 nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50 mg MSNs, ratio of MSNs to lipid (w/w) = 1:1.11, and ratio of lipid to CHO (w/w) = 3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48 ± 2.73) %, (30.70 ± 3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect.
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