ACS Applied Materials & Interfaces
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2017
·
IF 7.504
Ye Zhang,Congjun Zhang,Jing Chen,Li Liu,Mengyue Hu,Jun Li,Hong Bi
Multidrug resistance (MDR) has been recognized as a major obstacle to successful chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled drug delivery systems (DDS) are constructed to modulate drug efflux protein (P-gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug carrier due to its capability of inhibiting overexpression of P-gp and good amphiphilicity favorable for improving permeation and long-circulation property of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles-based DDS is developed to integrate chemotherapeutics delivery with fluorescence imaging functionalities on a comprehensive nanoplatform. The mitochondria-targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)-modified TPGS and fluorescent carbon quantum dots (CQDs) in an n-hexane/H2O mixed solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to 7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug-resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF-7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles can cause much more damage to cells of drug-resistant MCs. These results demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS have potential application in overcoming MDR of cancer cells as well as their MCs that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded CQDs-TPGS-TPP nanomicelles is also discussed.
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RSC Advances
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2016
·Vol. 6
·期 115
·113933-113939
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IF 3.289
Hongmei Liu,Yandong Xie,Yafei Zhang,Yifan Cai,Baiyang Li,Honglin Mao,Rutong Yu
Fe3O4 nanoparticles (NPs) have attracted a great deal of attention due to their magnetic properties, low toxicity, high surface area and their small sizes. Owning to the low toxicity, easy separation and controlled NPs size, in this study Fe3O4 NPs have been used for co-delivery two anticancer drugs for combination tumor therapy. We used doxorubicin (DOX) prodrugs and DSPE-PEG5000 to coat Fe3O4 NPs to form DOX–Fe3O4 NPs. The hydrophobic anticancer drug combretastatin A-4 (CA4) was loaded into DOX–Fe3O4 NPs to form DOX–CA4–Fe3O4 NPs. It was proved that the obtained DOX–CA4–Fe3O4 NPs with an average diameter around 53.7 ± 5.25 nm could accumulate effectively in tumors by an enhanced permeability and retention (EPR) effect. After intravenous injection, the DOX–CA4–Fe3O4 NPs were found to selectively accumulate at the tumor site and killed the cancer cells in a combinatorial way. The results indicate that the DOX–CA4–Fe3O4 NPs can be potentially applied as a safe and efficient two anticancer drugs delivery carrier.
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ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Hang Hu,Yihui Li,Qing Zhou,Yanxiao Ao,Chan Yu,Ying Wan,Huibi Xu,Zifu Li,Xiangliang Yang
Doxorubicin (DOX) is one of the most potent anticancer agents in cancer chemotherapy, but the clinical use of DOX is restricted by its severe side effects caused by nonspecific delivery. To alleviate the side effects and improve the antitumor efficacy of DOX, a novel redox-sensitive hydroxyethyl starch–doxorubicin conjugate, HES-SS-DOX, with diameter of 19.9 ± 0.4 nm was successfully prepared for tumor targeted drug delivery and GSH-mediated intracellular drug release. HES-SS-DOX was relatively stable under extracellular GSH level (∼2 μM) but released DOX quickly under intracellular GSH level (2–10 mM). In vitro cell study confirmed the GSH-mediated cytotoxicity of HES-SS-DOX. HES-SS-DOX exhibited prolonged plasma half-life time and enhanced tumor accumulation in comparison to free DOX. As a consequence, HES-SS-DOX exhibited better antitumor efficacy and reduced toxicity as compared to free DOX in the in vivo antitumor activity study. The redox-sensitive HES-SS-DOX was proved to be a promising prodrug of DOX, with clinical potentials, to achieve tumor targeted drug delivery and timely intracellular drug release for effective and safe cancer chemotherapy.
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MOLECULES
·
2024
·Vol. 29
·期 8
·1709
·
IF 4.2
Yanru Hu,Peng Liu
The diselenide bond has attracted intense interest in redox-responsive drug delivery systems (DDSs) in tumor chemotherapy, due to its higher sensitivity than the most investigated bond, namely the disulfide bond. Here, a diselenide-bridged doxorubicin dimeric prodrug (D-DOXSeSe) was designed by coupling two doxorubicin molecules with a diselenodiacetic acid (DSeDAA) molecule via α-amidation, as a redox-triggered drug self-delivery system (DSDS) for tumor-specific chemotherapy. The drug release profiles indicated that the D-DOXSeSecould be cleaved to release the derivatives selenol (DOX-SeH) and seleninic acid (DOX-SeOOH) with the triggering of high GSH and H2O2, respectively, indicating the double-edged sword effect of the lower electronegativity of the selenide atom. The resultant solubility-controlled slow drug release performance makes it a promising candidate as a long-acting DSDS in future tumor chemotherapy. Moreover, the interaction between the conjugations in the design of self-immolation traceless linkers was also proposed for the first time as another key factor for a desired precise tumor-specific chemotherapy, besides the conjugations themselves.
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International Journal of Nanomedicine
·
2018
·
IF 4.37
Abdul Hakeem,Fouzia Zahid,Guiting Zhan,Ping Yi,Hai Yang,Lu Gan,Xiangliang Yang
Background Nanotechnology-based drug delivery systems exhibit promising therapeutic efficacy in cancer chemotherapy. However, ideal nano drug carriers are supposed to be sufficiently internalized into cancer cells and then release therapeutic cargoes in response to certain intracellular stimuli, which has never been an easy task to achieve.Objective This study is to design mesoporous silica nanoparticles (MSNs)-based pH-responsive nano drug delivery system that is effectively internalized into cancer cells and then release drug in response to lysosomal/endosomal acidified environment.Methods We synthesized MSNs by sol-gel method. Doxorubicin (DOX) was encapsulated into the pores as a model drug. Polyaspartic acid (PAsA) was anchored on the surface of mesoporous MSNs (P-MSNs) as a gatekeeper via amide linkage and endowed MSNs with positive charge.Results In vitro release analysis demonstrated enhanced DOX release from DOX-loaded PAsA-anchored MSNs (DOX@P-MSNs) under endosomal/lysosomal acidic pH condition. Moreover, more DOX@P-MSNs were internalized into HepG2 cells than DOX-loaded MSNs (DOX@MSNs) and free DOX revealed by flow cytometry. Likewise, confocal microscopic images revealed that DOX@P-MSNs effectively released DOX and translocated to the nucleus. Much stronger cytotoxicity of DOX@P-MSNs against HepG2 cells was observed compared with DOX@MSNs and free DOX.Conclusion DOX@P-MSNs were successfully fabricated and achieved pH-responsive DOX release. We anticipated this nanotherapeutics might be suitable contenders for future in vivo cancer chemotherapeutic applications.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Yue Yang,Xiaoyu Lu,Qi Liu,Yu Dai,Xiaojie Zhu,Yanli Wen,Jiaqiu Xu,Yang Lu,Di Zhao,Xijing Chen,Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies. The liposomes (weight ratio of DOX to PA = 1:20, DOX 1 /PA 20 -LPs) exhibited the strongest synergistic effects, combination index was 0.38, 0.56, and 0.05 in MCF-7, HepG2, and A549 cells, respectively. In vitro cellular uptake study, the intercellular concentration of DOX in DOX 1 /PA 20 -LPs was 2.5-fold greater than DOX loaded liposome, and DOX 1 /PA 20 -LPs was taken in not only by macropinocytosis, but also by clathrin-mediated endocytosis. Intracellular distribution experiment showed that DOX 1 /PA 20 -LPs efficiently concentrated in the nucleus. In vivo studies indicated that co-encapsulated liposome not only showed the strongest antitumor ability by tumor growth suppression, but also significantly enhanced the safety by the change of body weight and reduced damages to other tissues (evidenced by histopathology study). These results indicated that DOX and PA co-delivery liposome successfully enhanced the anticancer efficacy and mitigated the toxicities of DOX, which displayed potential for clinical application with enhanced safety and efficacy.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Sijia Tian,Haoying Li,Yanxin Niu,Xueyan Hu,Yongxue Guo
Transcatheter arterial chemoembolization (TACE) is an important method in the treatment of liver cancer and identification of an ideal microsphere for embolization is a key step in its development. Here, we used a microfluidic device to prepare uniformly sized Photopolymerized pH-Responsive GelMA Microspheres with Doxorubicin Modification (DOX-GelMA) that integrated embolization and drug delivery properties. The acid-sensitive doxorubicin (DOX) prodrug was synthesized through a three-step reaction and coupled during curing of the microspheres under UV irradiation. The microspheres exhibited significant pH-responsive drug release in the tumor microenvironment and had a good degradation performance over 18 days. Microscopic images and scanning electron microscopy results showed that the microspheres had good sphericity and uniform particle size (96.61 ± 0.046 μm), and that the particle size and their degree of swelling were suitable for embolization therapy. In vitro cytotoxicity and blood compatibility experiments showed that the microspheres were good biocompatible. The drug-loaded microspheres had obvious inhibitory effect on HepG2. A rabbit ear embolization study demonstrated that the microspheres could effectively block arterial blood flow. The DOX-GelMA microspheres simultaneously achieved physical targeted therapy and chemotherapy, and had great prospects in TACE therapy.
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CARBOHYDRATE POLYMERS
·
2013
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IF 3.479
Minghui Xu,Junmin Qian,Aili Suo,Hongjie Wang,Xueqing Yong,Xuefeng Liu,Rongrong Liu
To minimize the side effect of chemotherapy, a novel reduction/pH dual-sensitive drug nanocarrier, based on PEGylated dithiodipropionate dihydrazide (TPH)-modified hyaluronic acid (PEG-SS-HA copolymer), was developed for targeted delivery of doxorubicin (DOX) to hepatocellular carcinoma. The copolymer was synthesized by reductive amination via Schiff's base formation between TPH-modified HA and galactosamine-conjugated poly(ethylene glycol) aldehyde/methoxy poly(ethylene glycol) aldehyde. Conjugation of DOX to PEG-SS-HA copolymer was accomplished through the hydrazone linkage formed between DOX and PEG-SS-HA, and confirmed by FTIR and 1 H NMR spectra. The polymer–DOX conjugate could self-assemble into spherical nanoparticles (∼150 nm), as indicated by TEM and DLS. In vitro release studies showed that the DOX-loaded nanoparticles could release DOX rapidly under the intracellular levels of pH and glutathiose. Cellular uptake experiments demonstrated that the nanoparticles could be efficiently internalized by HepG2 cells. These results indicate that the PEG-SS-HA copolymer holds great potential for targeted intracellular delivery of DOX.
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DRUG DELIVERY
·
2020
·
IF 4.902
Chunyun Wang,Peilan Qi,Yan Lu,Lei Liu,Yanan Zhang,Qianli Sheng,Tianshun Wang,Mengying Zhang,Rui Wang,Shiyong Song
The Editors and Publisher of the journal Drug Delivery, have retracted the following article:Chunyun Wang, Peilan Qi, Yan Lu, Lei Liu, Yanan Zhang, Qianli Sheng, Tianshun Wang, Mengying Zhang, Rui Wang & Shiyong Song (2020) Bicomponent polymeric micelles for pH-controlled delivery of doxorubicin, Drug Delivery, 27:1, 344–357, DOI: 10.1080/10717544.2020.1726526Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to fully address the concerns raised. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2015
·
IF 3.368
Longlong Zhang,Pei Zhang,Qingyun Zhao,Yongchun Zhang,Longqiao Cao,Yuxia Luan
An amphiphilic anionic polypeptide , methoxypolyethylene glycol–poly (glutamic acid) (mPEG–PGA), was synthesized, characterized and evaluated as a nanocarrier for the cationic anticancer drug doxorubicin hydrochloride (DOX·HCl). The complex self-assembled into nanorods in aqueous solutions via electrostatic interactions and exhibited a superior drug loading content (50.8%) and drug loading efficiency (90.2%). The average major axis of the drug-loaded nanorods was approximately 300 nm, as determined by transmission electron microscopy . An in vitro release assay showed that drug-loaded nanorods exhibited pH-sensitivity and sustained release. Haemolysis assays demonstrated that the polypeptide was haemocompatible, and the polypeptide drug carrier significantly reduced the haemolysis ratio of DOX·HCl. The pharmacokinetics study showed that DOX-loaded nanorods significantly prolonged the resident time in blood. An in vitro cytotoxicity study and cellular uptake assays demonstrated that the DOX-loaded nanorods resulted in higher cell proliferation inhibition and a higher level of tumour cell uptake in A549 cells than with free DOX·HCl. The prolonged circulation and enhanced antitumor efficacy of DOX-loaded nanorods shows promise for efficient cancer chemotherapy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Li Wang,Dongli Yu,Rui Dai,Duo Fu,Wenzhe Li,Zhaoming Guo,Changhao Cui,Jianqiang Xu,Song Shen,Kun Ma
Graphene oxide (GO) owns huge surface area and high drug loading capacity for aromatic molecules, such as doxorubicin (DOX). However, its biocompatibility is poor and it might agglomerate in physiological conditions. Chemical modification of GO with hydrophilic polymer, especially PEGylation , was a common method to improve its biocompatibility. But the chemical modification of GO was complicated, and its drug loading capacity might be reduced because of the occupation of its functional groups. In this study, DOX-PEG polymers with different PEG molecular weights were synthesized to modify nano graphene oxide (NGO) to simultaneously realize the solubilization of NGO and the high loading capacity of DOX. The result showed that the drug release of NGO@DOX-PEG was pH sensitive. NIR irradiation could augment the drug release, cellular uptake, cytotoxicity and nuclear translocation of nanodrugs. Among the three kinds of nanodrugs, NGO@DOX-PEG5K was superior to others. It suggested that after conjugating with PEG, the bond between DOX-PEG and NGO was weakened, which resulted in a better drug release and treatment effect. In summary, the NIR and pH dual-responsive NGO@DOX-PEG nanodrugs were developed by noncovalent modification, and it demonstrated excellent biocompatibility and photochemical therapeutic effect, presenting a promising candidate for antitumor therapy, especially NGO@DOX-PEG5K.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Qin-Qin Gao,Chuan-Min Zhang,En-Xia Zhang,Hui-Ying Chen,Yu-Hong Zhen,Shu-Biao Zhang,Shu-Fen Zhang
As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.
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