RSC Advances
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2015
·Vol. 5
·期 115
·94719-94731
·
IF 3.84
Lili Chen,Xiaohong Wang,Fangling Ji,Yongming Bao,Jingyun Wang,Xianwu Wang,Lianying Guo,Yachen Li
Combined treatment of drugs and therapeutic genes has emerged as a new modality of anticancer therapy. In this study, a new amphiphilic bifunctional pullulan derivative (named as PSP) containing stearic acid and low-molecular weight (1 kDa) branched polyethylenimine was prepared and evaluated as a nano-carrier for the co-delivery of a drug and gene for potential cancer therapy. The amphiphilic PSP could self-assemble into cationic core–shell nano-micelles in water, with a critical micelle concentration of around 58.9 mg L−1. PSP nanomicelles had an average size of 188.75 ± 3.18 nm, and a positive zeta potential of 17.83 ± 0.75 mV. The drug loading content and encapsulation efficiency of the PSP nanomicelles for doxorubicin (DOX), an anti-tumor drug, were about 5.10% and 56.07%, respectively, and DOX in PSP nanomicelles showed sustained release. The flow cytometry and confocal laser scanning microscopy showed that PSP/DOX nanomicelles could be successfully internalized by MCF-7 cells. The in vitro IC50 of PSP/DOX nanomicelles was slightly lower than that of free DOX against MCF-7 cells. Additionally, PSP nanomicelles condensed DNA efficiently to form compact structures, and induced comparable GFP gene expression level to Lipo2000 at N/P = 10 in gene transfection studies. In comparison with single DOX or p53 delivery, the co-delivery of DOX and therapy gene p53 using PSP micelles displayed higher cytotoxicity and induced a higher apoptosis rate of tumor cells in vitro. Moreover, PSP exhibited good blood compatibility and low cytotoxicity in the hemolysis and MTT assays, respectively. Altogether, PSP nanomicelles have a great potential in delivering hydrophobic anticancer drugs and therapeutic genes simultaneously for improved cancer therapy.
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2015
·Vol. 36
·期 3
·873-880
·
IF 2.088
Yu Lou,Zhen Wang,Yi Xu,Ping Zhou,Junxian Cao,Yuanshi Li,Yeping Chen,Junfeng Sun,Lu Fu
Treatment with doxorubicin (DOX) is one of the major causes of chemotherapy-induced cardiotoxicity and is therefore, the principal limiting factor in the effectiveness of chemotherapy for cancer patients. DOX‑induced heart failure is thought to result from endoplasmic reticulum (ER) stress and cardiomyocyte apoptosis. Resveratrol (RV), a polyphenol antioxidant found in red wine, has been shown to play a cardioprotective role. The aim of the present study was to examine the effects of RV on DOX‑induced cardiotoxicity in H9c2 cells. We hypothesized that RV would protect H9c2 cells against DOX‑induced ER stress and subsequent cell death through the activation of the Sirt1 pathway. Our results demonstrated that the decrease observed in the viability of the H9c2 cells following exposure to DOX was accompanied by a significant increase in the expression of the ER stress‑related proteins, glucose‑regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). However, we found that RV downregulated the expression of ER stress marker protein in the presence of DOX and restored the viability of the H9c2 cells. Exposure to RV or DOX alone only slightly increased the protein expression of Sirt1, whereas a significant increase in Sirt1 protein levels was observed in the cells treated with both RV and DOX. The Sirt1 inhibitor, nicotinamide (NIC), partially neutralized the effects of RV on the expression of Sirt1 in the DOX‑treated cells and completely abolished the effects of RV on the expression of GRP78 and CHOP. The findings of our study suggest that RV protects H9c2 cells against DOX‑induced ER stress through ER stabilization, and more specifically through the activation of the Sirt1 pathway, thereby leading to cardiac cell survival.
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BIOMACROMOLECULES
·
2024
·
IF 5.5
Yuhan Yang,Yangyi Chen,Yue Wei,Wei Wu,Qing Wang,Tianyun Xue,Xiaoyan Zhang,Wei Chen,Wei Zhang
A drug delivery system based on silybin-conjugated chitosan (CS-SB) polymeric micelles was developed to improve the oral absorption of doxorubicin (DOX). SB was grafted to CS via succinic acid, and CS-SB was identified by 1H NMR and FT-IR. The DOX-loaded micelles were prepared by self-assembly, and the characteristics of micelles, including a small particle size of 167.8 ± 2.3 nm, a high drug loading capacity of 8.59%, and a low critical micelle concentration of 1.3 × 10–5 g/mL, were demonstrated. The micelles showed oral bioavailability of up to 193% versus DOX·HCl. The cytotoxicity test showed the biosafety of CS-SB and the potential of reductive DOX-induced cardiotoxicity. The inhibition of P-gp efflux and CYP3A4 enzyme in CS-SB micelles was confirmed by cellular uptake and enzyme activity inhibition tests. The endocytosis process of micelles was revealed by an endocytosis inhibition test. The findings exhibited the potential of CS-SB micelles in drug delivery.
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Advanced Healthcare Materials
·
2014
·Vol. 3
·期 11
·1877-1888
·
IF 4.88
Mingqiang Li,Zhaohui Tang,Jian Lin,Yu Zhang,Shixian Lv,Wantong Song,Yubin Huang,Xuesi Chen
The multi-modal combination therapy is proved powerful and successful to enhance the antitumor efficacy in clinics as compared with single therapy modes. In this study, the potential of combining chemotherapy with antiangiogenic therapy for the treatment of non-small-cell lung cancer is explored. Towards this aim, OEGylated carboxymethyl cellulose–(2-(2-(2-methoxyethoxy)ethoxy)methyl)oxirane (CMC–ME 2 MO) is prepared by treating CMC with ME 2 MO in the alkaline aqueous solution, and used to efficiently carry doxorubicin (DOX) with high drug-loading content (16.64%) and encapsulation efficiency (99.78%). As compared to free DOX, the resulting nanoparticles show not only the favorable stability in vitro but also the prolonged blood circulation, improved safety and tolerability, optimized biodistribution, reduced systemic toxicity, and enhanced antitumor efficacy in vivo, indicates a potential utility in cancer chemotherapy. Furthermore, the combination of the DOX-loaded polysaccharide nanoparticles and antiangiogenic drug endostar provides synergistic effects of chemotherapy and antiangiogenic therapy, which shows the highest efficiency in tumor suppression. The combination approach of the DOX-containing nanomedicine and endostar for efficient treatment of non-small-cell lung cancer is first proposed to demonstrate the synergistic therapeutic effect. This synergistic combination proves to be a promising therapeutic regimen in cancer therapy and holds great potential for clinical application.
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Regenerative Biomaterials
·
2021
·Vol. 8
·期 5
·
IF 6.353
Liu Boxun,Jin Zhizhong,Chen Haiyan,Liang Lun,Li Yao,Wang Guo,Zhang Jing,Xu Tao
Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared with blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically approved poly (L-lactic acid)/gelatine membrane for local and long-term delivery of DOX for the treatment of glioblastoma.
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NANOTECHNOLOGY
·
2017
·Vol. 28
·期 8
·085603
·
IF 3.44
Xiaoqing Yi,Dan Zhao,Quan Zhang,Jiaqi Xu,Gongdao Yuan,Renxi Zhuo,Feng Li
Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Yan Zhang,Chang Wei,Feng Lv,Tianjun Liu
Elucidation of the pathway of drug delivery and carrier degradation in vivo is essential for the fabrication of a feasible drug delivery system. Multispectral fluorescence imaging can track a drug delivery system simultaneously based on the separation of fluorescence at multiple wavelengths without interference. In this study, the Doxorubicin loaded genipin-crosslinked globin and PEI nanoparticles (Gb-G-PEI/Dox NPs) were designed as a dual fluorescent drug delivery system to track the drug release and carrier degradation process. Both confocal laser scanning microscopy and flow cytometric results showed that Gb-G-PEI/Dox NPs had a higher cellular uptake efficiency than Doxorubicin in the Bel-7402 cell line due to its small size and positively charged surface. The in vivo metabolism experiments tracked by the multispectral fluorescence imaging system elucidated the sustained drug release and carrier degradation process of the Gb-G-PEI/Dox NPs. Furthermore, the in vivo antitumor effects study by the bioluminescence imaging showed that Gb-G-PEI/Dox NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. As a result, Gb-G-PEI/Dox NPs were demonstrated to be a highly efficient, feasible and visible drug delivery system for tumor therapy.
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BIOCONJUGATE CHEMISTRY
·
2017
·
IF 4.818
Daquan Wang,Yibo Ren,Yongping Shao,Demei Yu,Lingjie Meng
We developed a bifunctional nanoplatform for targeted synergistic chemo–photothermal cancer treatment. The nanoplatform was constructed through a facile method in which poly(N-vinyl pyrrole) (PVPy) was coated on cut multiwalled carbon nanotubes (c-MWNTs); FA-PEG-SH was then linked by thiol–ene click reaction to improve the active targeting ability, water dispersibility, and biocompatibility and to extend the circulation time in blood. The PVPy shell not only enhanced the photothermal effect of c-MWNTs significantly but also provided a surface that could tailor targeting molecules and drugs. The resulting MWNT@PVPy-S-PEG-FA possessed high drug-loading ratio as well as pH-sensitive unloading capacity for a broad-spectrum anticancer agent, doxorubicin. Owing to its outstanding efficiency in photothermal conversion and ability in targeted drug delivery, the material could potentially be used as an efficient chemo–photothermal therapeutic nanoagent to treat cancer.
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Polymers
·
2018
·Vol. 10
·期 10
·1127
·
IF 2.935
Yinglei Zhai,Xing Zhou,Zhiqiang Zhang,Lei Zhang,Dianyu Wang,Xinhui Wang,Wei Sun
The side effects of doxorubicin (DOX) extremely limit its application in the treatment of malignant tumors. Nano-sized polymeric drugs based on the acidic microenvironment of tissular- or intra- tumor have attracted ample attention because of their potential in reducing side effects. In this research, an amphiphilic diblock copolymer based on poly (ethylene glycol) (PEG) and functionalized polycaprolactone (PCL) was synthesized and utilized as the drug carrier. DOX was chemically conjugated with the polymer via acid-cleavable imine bonds to obtain a novel pH-sensitive DOX prodrug (mPEG-PCL-Imi-DOX). mPEG-PCL-Imi-DOX (24.2 wt % DOX content) formed micelles with an average diameter of 125 nm through a simple solvent evaporation method. The in vitro release profile demonstrated that DOX release of the prodrug micelles was pH-responsive and able to be accelerated with the decrease of pH. In vitro cytotoxicity assay tests revealed that the pH-sensitive DOX prodrug micelles exhibited relatively lower toxicity and similar antitumor efficacy towards MCF-7 cells compared with free DOX. Hence, the DOX prodrug micelles with imine bonds can offer a carrier with great potential for chemo-therapeutics.Keywords:doxorubicin;pH-sensitive;prodrug;micelles;imine
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Nanoscale
·
2021
·Vol. 13
·期 19
·8998-9008
·
IF 7.79
Xupeng Mu,Meng Zhang,Anhui Wei,Fei Yin,Yan Wang,Kebang Hu,Jinlan Jiang
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA–DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA–DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA–DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
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Pharmaceutics
·
2026
·Vol. 18
·期 7
·816
·
IF 6.9
Luyao Ma,Fulai Chen,Qinghao Xu,Jianwei Yu,Yang Liu,Lei Duan
Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform.Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis.Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells.Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo.
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ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yudian Qiu,Jie Bai,Yecheng Feng,Xiaojing Shi,Xubo Zhao
Synergistic therapy holds promising potential in cancer treatment. Here, the inclusion of catechol moieties, a disulfide cross-linked structure, and pendent carboxyl into the network of polymeric nanogels with glutathione (GSH)-responsive dissociation and pH-sensitive release is first disclosed for the codelivery of doxorubicin (DOX) and bortezomib (BTZ) in synergistic cancer therapy. The pendent carboxyl groups and catechol moieties are exploited to absorb DOX through electrostatic interaction and conjugate BTZ through boronate ester, respectively. Both electrostatic interactions and boronate ester are stable at neutral or alkaline pH, while they are instable in an acidic environment to further recover the activities of BTZ and DOX. The polymeric nanogels possess a superior stability to prevent the premature leakage of drugs in a physiological environment, while their structure is destroyed in response to a typical endogenous stimulus (GSH) to unload drugs. The dissociation of the drug-loaded nanogels accelerates the intracellular release of DOX and BTZ and further enhances the therapeutic efficacy. In vitro and in vivo investigations revealed that the dual-drug loaded polymeric nanogels exhibited a strong ability to suppress tumor growth. This study thus proposes a new perspective on the production of multifunctional polymeric nanogels through the introduction of different functional monomers.
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