COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Tingxian Liu,Mingfang Wang,Tianqi Wang,Yao Yao,Na Zhang
The greatest challenge in combining chemotherapy and gene therapy is the construction of a suitable platform for the co-delivery of the drug and the therapeutic gene. In this study, a simplified and effective system for the co-loading and intracellular co-delivery of doxorubicin (Dox) and siRNA was developed. Oligodeoxynucleotides with CGA repeating units (CGA-ODNs) were introduced to load Dox. The loading mechanism was based on the ability of Dox to intercalate within double-stranded 5′-GC-3′ or 5′-CG-3′ sequences. Poly(ethyleneimine) (PEI) was used to condense siRNA and Dox loaded CGA-ODNs (CGA-ODNs-Dox) to obtain Dox and siRNA co-loaded nanocomplexes (PEI/CGA-ODNs-Dox&siRNA, PDR). The cellular uptake of PDR in A549 and HepG2 cells was 39.52% and 36.78%, respectively, indicating that the co-loading and co-delivery effect was achieved through the mono-loading method. An in vitro drug release study indicated that CMCS-poly(ethylene glycol) (PEG)-NGR (CPN) modified PDR (CPN-PDR) displayed a pH-triggered drug release property due to the reversed surface charge of CMCS in an acidic environment. Cellular uptake studies also confirmed that the disassembly of CPN-PDR was induced by an acidic pH in the extracellular matrix. Moreover, lysosomal escape of both Dox and siRNA was observed. Successful accumulation of Dox in the cell nucleus and siRNA in the cytoplasm was also demonstrated. Consequently, the novel construction of a simplified loading method and high co-delivery efficiency was proven to be a promising platform for the co-delivery of drug and siRNA.
研究领域:
药学
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分子生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 128
·105901-105907
·
IF 3.84
Guan-Hai Wang,Hui-Kang Yang,Yi Zhao,Da-Wei Zhang,Li-Ming Zhang,Jian-Tao Lin
In this work, novel biodegradable cationic micelles were prepared based on poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) and chitosan (CS) by click reaction, and applied for co-delivery of doxorubicin (DOX) and p53 plasmid. The structure of the copolymer was characterized by 1H NMR and FTIR. The loading amount of DOX in the micelles was 12.8%. Fluorescence spectra confirmed that DOX interacted via π–π stacking with micelles when DOX was encapsulated into the micelles. In particular, its complexation with plasmid DNA was investigated using agarose gel electrophoresis, flow cytometry, zeta potential, and particle size analyses as well as transmission electron microscopy observations. The results showed that the copolymers have a strong pDNA condensation ability and provide protection of pDNA against deoxyribonuclease I degradation. CS-g-PZLL/DOX/p53 nanoparticles showed good gene transfection efficiency in vitro. Fluorescence images and flow cytometry tests revealed that p53 and DOX could be efficiently transported into Hela tumor cells simultaneously, and the optimum N/P ratio for p53 transfection was 20/1. For co-delivery analysis, the obtained CS-g-PZLL/DOX/p53 complexes showed a better inhibitory effect on Hela tumor cells than DOX or p53 used singly.
研究领域:
药剂学
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肿瘤学
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生物材料学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Qian Li,Shixian Lv,Zhaohui Tang,Muhua Liu,Dawei Zhang,Yan Yang,Xuesi Chen
Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·HCl) based on methoxypoly(ethylene glycol)- block -poly( l -glutamic acid) (mPEG- b -PLG) for cancer treatment. PTX was grafted to the mPEG- b -PLG by esterification to give mPEG- b -PLG- g -PTX. DOX·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG- b -PLG- g -PTX in aqueous solution. The release rate of DOX·HCl from the drug-loaded nanoparticles (mPEG- b -PLG- g -PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG- b -PLG- g -PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG- b -PLG- g -PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX·HCl and mPEG- b -PLG- g -PTX. These results indicated that the mPEG- b -PLG- g -PTX-DOX would have great potential in cancer therapy.
研究领域:
药剂学
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Jiadong Pang,Baoxiong Zhuang,Li-Ming Zhang
Pancreatic cancer is one of the most lethal malignancies in the world and remains one of the leading causes of cancer related death. For its treatment, a lot of investigations have dealt not only with individual chemotherapy by using polymeric carriers to deliver anticancer drugs, but also with individual gene therapy by using polymeric carriers to deliver nucleic acids such as small interfering RNA (siRNA) and plasmid DNA . However, relatively few studies have been focused on the co -delivery of gene and anticancer drug by multifunctional polymeric carriers for its synergistic therapy. In this work, a DPLL-functionalized amylose (ADP) was prepared by the click reaction between azidized amylose and propargyl focal point poly( l -lysine) dendrons, and then used to co-deliver plasmid pIRES2-EGFP-TNFα and curcumin for pancreatic cancer treatment. Due to the internal hydrophobic cavity of amylose component, ADP could load efficiently curcumin with anticancer activity and showed a sustained release behavior. Moreover, the curcumin-loaded ADP could form colloidally stable nanocomplexes with plasmid DNA in aqueous system due to the existence of cationic poly( l -lysine) dendrons and exhibited high gene transfection efficiency. The in vitro and in vivo tests confirmed the effectiveness of using ADP to co-deliver plasmid pIRES2-EGFP-TNFα and curcumin for synergistic therapy of pancreatic cancer.
研究领域:
生物材料学
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肿瘤学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Feifei Wang,Dianlong Jia,Qingcui Song,Xiaomeng Lu,Guozi Xia,Jun Li,Xiaodong Jia,Mingliang Gu,Fengjiao Yuan,Zhengping Wang,Zhangyong Xia
Resistance against tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death of cancer cells is a major obstacle in clinical application of TRAIL. Bortezomib (BTZ) is the first-generation proteasome inhibitor to enhance TRAIL-mediated apoptosis and overcome tumor cell resistance to TRAIL, therefore we developed a novel nanodrug called LSBTZ-TRAIL to co-deliver TRAIL and BTZ via liposomes. TRAIL was coupled to the surface of the liposome by DSPE-PEG 2000 -NHS, while BTZ was encapsulated in the internal aqueous phase. LSBTZ-TRAIL was characterized with a particle size of 147.00 ± 1.300 nm, polydispersity index (PDI) of 0.056 ± 0.005 and zeta potential of -8.17 ± 0.600 mV. LSBTZ-TRAIL did not change the secondary structure of TRAIL, and LSBTZ-TRAIL was stable in 50% fetal bovine serum and tumor microenvironment. In vitro, the cell killing capacity of LSBTZ-TRAIL was 1.16-6.22 times that of TRAIL + BTZ. Mechanistically, LSBTZ-TRAIL induced apoptosis of tumor cells by up-regulating the death receptor (DR4/5) and activating the caspase signaling pathway. In vivo and in vitro uptake experiments, LS-TRAIL accumulated more in tumor cells or tissues than LS. In vivo , the antitumor effect of LSBTZ-TRAIL was 2.62 times that of TRAIL + BTZ, and prolonged the survival and blood circulation time of mice. In addition, safety evaluation showed that LSBTZ-TRAIL had no acute toxic effects in vivo . These results suggested that the liposomal co-delivery system of TRAIL and BTZ significantly enhance their antitumor effects and provide a new approach to overcome TRAIL-resistance.
研究领域:
肿瘤学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Micro & Nano Letters
·
2025
·Vol. 20
·期 1
·e70008
·
IF 2.4
Xiuping Shen,Aiyong Zhu,Yafeng Xu
Doxorubicin (DOX), an anthracycline antibiotic, is widely used to treat a range of solid tumours and haematological malignancies. However, its clinical application in breast cancer is hindered by toxic side effects and the development of multidrug resistance (MDR). Enhancing the selective targeting of DOX and overcoming MDR are critical to improving treatment efficacy. Here, we present a DNA nanoflower (DNF)-based delivery system, designed via rolling circle amplification and multi-primer amplification (MCA), which co-delivers antisense oligonucleotides (ASOs) and DOX to human breast cancer cells (MCF-7). This system, named DNF-ASO@DOX, effectively promotes gene silencing, enhances drug accumulation and significantly inhibits cell proliferation. Furthermore, in vivo studies using mouse models of breast cancer demonstrated potent therapeutic effects, highlighting DNF-ASO@DOX as a promising strategy for enhanced anti-tumour therapy.
研究领域:
生物医学工程
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肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Tao Liu,Xidong Wu,Shaohua Chen,Peina Wu,Hong Han,Hongbin Zhang,Junzheng Li,Guanxue Li,Siyi Zhang
To obtain a high-efficiency drug and gene co-delivery system to HNE-1 tumor therapy, a polymeric prodrug (PAAs-MTX) with chemotherapeutic sensibilization was synthesized consisting of a GSH-response hyperbranched poly(amido amine) (PAAs) and an antitumor drug of methotrexate (MTX). Then, the targeting molecule to HNE-1 cells, transferrin (Tf), was conjugated to form the Tf-PAAs-MTX. This polymeric prodrug could deliver MMP-9 shRNA plasmid (pMMP-9) again to form the drug and gene co-delivery system of Tf-PAAs-MTX/pMMP-9. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency to HNE-1 cells. Besides that, Tf-PAAs-MTX also showed the chemotherapeutic sensibilization effect, the formulation containing PAAs segments showed much higher cytotoxicity than that of free MTX. Benefiting from the sensibilization effect and MTX/pMMP-9 co-delivery strategy, this Tf-PAAs-MTX/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. Moreover, its biocompatibility, especially the blood compatibility was analyzed. This polymeric prodrug provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization and targeting into one single platform, which showed a promising application in nasopharyngeal carcinoma therapy.
研究领域:
肿瘤学
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药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2015
·
IF 3.84
Hui Zhao,Zhen Wei,Shuxin Xu,Minjie Tang,Liandong Deng,Jianhua Zhang,Anjie Dong
Combining functions of multidrug co-delivery and multistep release in biocompatible membranes is an oncoming requirement for improving therapeutic process. In this paper, a kind of polymer micelle-embedded core/shell nanofibrous membranes was prepared by a simple and effective technology of coaxial electrospinning. The nanofibers were composed of hydrophobic polycaprolactone (PCL) shell layer and hydrophilic polyvinyl pyrrolidone (PVP) core in which more than 40 % (w/w) amphiphilic block copolymer mPECT micelles (mPECT Ms) were embedded. Two bioactive drugs, lincomycin hydrochloride (LH) as the anti-inflammatory drug and Vitamin E (VE) as the fibrinolysis drug, were effectively loaded in the PVP core of the fibers and mPECT Ms, respectively. The SEM and TEM figures showed the smooth core/shell nanofibers with interiorly even-distributed micelles were fabricated. The XRD patterns illustrated that drugs distributed amorphously in the composite mats without crystallization. The in vitro degradation test also gave evidence to the time consistency between the degradation time of this material and potential occurrence time of adhesion. Furthermore, the in vitro release profiles indicated that both drugs were controlled to release sustainably for more than 15 days, and multistep release pattern of the early fast release of LH companied by the slow VE release was achieved. Therefore, the polymer micelle-embedded core/shell nanofibrous membranes could provide a new strategy for therapeutic application to realize multidrug co-delivery and multistep release.
研究领域:
生物材料学
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药物递送系统
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Lian Deng,Xiongjie Zhu,Zhongjian Yu,Ying Li,Lingyu Qin,Zhile Liu,Longbao Feng,Rui Guo,Yanfang Zheng
Background Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer.Methods Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model.Results T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model.Conclusion The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.
研究领域:
纳米医学
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肿瘤学
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药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 19
·6972
·
IF 4.6
Zheng Huang,Tong Xian,Xiangyi Meng,Huaisong Hu,Lixia Gao,Jiuhong Huang,Donglin Yang,Kepeng Ou,Bochu Wang,Yimei Zhang
Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that has been widely used for anti-tumor therapy by the generation of excessive highly cytotoxic ROS. However, the poor water solubility of the photosensitizer, reactive oxygen species (ROS) depleting by high concentrations of glutathione (GSH) in the tumor microenvironment and the activation of DNA repair pathways to combat the oxidative damage, will significantly limit the therapeutic effect of PDT. Herein, we developed a photosensitizer prodrug (CSP) by conjugating the photosensitizer pyropheophorbide a (PPa) and the DNA-damaging agent Chlorambucil (Cb) with a GSH-responsive disulfide linkage and demonstrated a multifunctional co-delivery nanoplatform (CSP/Olananoparticles (NPs)) together with DSPE-PEG2000and PARP inhibitor Olaparib (Ola). TheCSP/Ola NPsfeatures excellent physiological stability, efficient loading capacity, much better cellular uptake behavior and photodynamic performance. Specifically, the nanoplatform could induce elevated intracellular ROS levels upon the in situ generation of ROS during PDT, and decrease ROS consumption by reducing intracellular GSH level. Moreover, theCSP/Ola NPscould amplify DNA damage by released Cb and inhibit the activation of Poly(ADP-ribose) polymerase (PARP), promote the upregulation of γ-H2AX, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. In vitro investigations revealed thatCSP/Ola NPsshowed excellent phototoxicity and the IC50values ofCSP/Ola NPsagainst MDA-MB-231 breast cancer cells were as low as 0.05–01 μM after PDT. As a consequence, the co-delivery nanoplatform greatly promotes the tumor cell apoptosis and shows a high antitumor performance with combinational chemotherapy and PDT. Overall, this work provides a potential alternative to improve the therapeutic efficiency of triple negative breast cancer cell (TNBC) treatment by synergistically enhancing DNA damage and disrupting DNA damage repair.Keywords:chemo-photodynamic therapy;DNA damage repair;PARP inhibitor;co-delivery;GSH-responsive
研究领域:
癌症治疗
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Jing Zhang,Jian Han,Xiuli Zhang,Jing Jiang,Maolei Xu,Daolai Zhang,Jingtian Han
An amphiphilic all- trans -retinoic acid (ATRA)–chitooligosaccharide (RCOS) conjugate was synthesized to form self-assembled polymeric nanoparticles to facilitate the co-delivery of ATRA and paclitaxel (PTX). The blank RCOS nanoparticles possessed low hemolytic activity and cytotoxicity, and could efficiently load PTX with a drug loading of 22.2% and a high encapsulation efficiency of 71.3%. PTX-loaded RCOS nanoparticles displayed a higher cytotoxicity to HepG2 cells compared to PTX plus ATRA solution when corrected by the accumulated drug release. Cellular uptake profiles of RCOS nanoparticles were evaluated via confocal laser scanning microscope and flow cytometry with FITC as a fluorescent mark. The RCOS nanoparticles could be rapidly and continuously taken up by HepG2 cells via endocytosis and transported into the nucleus, and the uptake rates increased with particle concentration. These results revealed the promising potential of RCOS nanoparticles as drug carriers for co-delivery of ATRA and PTX or other hydrophobic therapeutic agents.
研究领域:
药剂学
·
生物材料学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Xiaoyan Zhou,Qianqian Zheng,Changyong Wang,Jiake Xu,Jian-Ping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.
研究领域:
药物学
·
癌症研究
·
聚合物化学
·
基因治疗
✓ 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）