Molecular Medicine Reports
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2023
·Vol. 28
·期 2
·1-11
·
IF 3.4
Qiao Lu,Xueyang Gong,Guangtao Jia,Jingliang Wu,Siwei Liu,Ke Song,Guixiang Tian
All‑trans retinoic acid (ATRA) has been implicated in the differentiation of hepatic stellate cells (HSCs). In the present study, the liver‑targeting hyaluronic acid micelles (ADHG) were prepared for co‑delivery of ATRA and doxorubicin (DOX) to block the HSC‑hepatoma interrelation. To simulate the tumor microenvironment, an in vitro dual‑cell model and an in vivo co‑implantation mouse model were established for anticancer studies. The experimental methods involved the MTT assay, wound‑healing assay, cellular uptake, flow cytometry and and in vivo antitumor study. The results revealed that the HSCs in the research models notably promoted tumor proliferation and migration. Furthermore, ADHG were readily internalized by cancer cells and HSCs simultaneously, and widely distributed in cancer regions. The in vivo antitumor studies demonstrated that ADHG could notably decrease HSC activation and extracellular matrix deposition, as well as constrain tumor growth and metastasis. Therefore, ATRA could facilitate DOX‑induced anti‑proliferation and anti‑metastasis effects, and ADHG are a promising nano‑sized formulation for the combination therapy of hepatocellular carcinoma.
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RSC Advances
·
2016
·Vol. 6
·期 32
·27102-27112
·
IF 3.289
Lei Li,Beibei Lu,Qikui Fan,Lulu Wei,Jianning Wu,Jun Hou,Xuhong Guo,Zhiyong Liu
In this work, well-defined pH-responsive methoxy poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly[2-(dimethylamino)ethyl methacrylate]-g-7-propinyloxy coumarin triblock amphiphilic copolymers (mPEG-b-PCL-b-PDMAEMA-g-PC) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and click chemistry. The chemical structures and compositions of these copolymers were characterized using Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR). The molecular weights of the copolymers were obtained using 1H NMR spectroscopy and gel permeation chromatography (GPC) measurements. Subsequently, the polymers could self-assemble into micelles which were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescence spectroscopy. The pH-responsive self-assembly behavior of these triblock copolymers in water were investigated at different pH values of 5 and 7.4 for controlled doxorubicin release, the results indicated that the release rate of DOX could be effectively controlled by altering the pH, DOX was sealed in neutral surroundings and DOX release was triggered in acidic surroundings. CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the micelles had no associated cytotoxicity, possessed good biodegradability and biocompatibility, and identified the location of the DOX in HeLa cells. The DOX-loaded micelles possessed high cytotoxicity to HeLa cells and exhibited inhibition of the proliferation of HeLa cells. Moreover, these flexible micelles with an on–off switched drug release may offer a promising pattern to deliver a wide variety of hydrophobic payloads to tumor cells for cancer therapy.
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BIOMACROMOLECULES
·
2018
·
IF 5.738
Weitong Sun,Xiaoyan Chen,Chao Xie,Yong Wang,Liteng Lin,Kangshun Zhu,Xintao Shuai
Drug resistance, developed through multiple mechanisms, is a major hindrance to successful chemotherapy of tumor. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy which may improve anticancer effect by synergistic actions. In this study, triblock copolymer of poly(ethylene glycol)-block-poly(l-lysine)-block-poly aspartyl (N-(N′,N′-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to not only bypass drug efflux but also down-regulate the antiapoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift drug release at tumors. The codelivered siRNA serves to suppress the expression of antiapoptotic BCL-2 and hence sensitize the cancer cells to anticancer drugs and produce improved therapeutic effect. Consequently, the codelivery of BCL-2 siRNA and anticancer drug DOX serves as a promising strategy against drug resistance in chemotherapy.
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MACROMOLECULAR BIOSCIENCE
·
2014
·Vol. 14
·期 10
·1415-1428
·
IF 3.65
Xiaoyu Ai,Jin Sun,Lu Zhong,Chunnuan Wu,Handong Niu,Tao Xu,He Lian,Xiaopeng Han,Guolian Ren,Wenya Ding,Jia Wang,Xiaohui Pu,Zhonggui He
A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P 5k SSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P 5k LV (P 5k LV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P 5k SSLV-DOX, P 5k LV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P 5k SSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P 5k LV-DOX nanomicelles. In conclusion, the redox-responsive P 5k SSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.
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Analytical Methods
·
2018
·Vol. 11
·期 4
·443-453
·
IF 2.073
Pramod K. Kalambate,Yankai Li,Yue Shen,Yunhui Huang
In this work, a novel highly sensitive electrochemical sensing platform has been developed for simultaneous determination of anticancer drugs doxorubicin (DOX) and dasatinib (DAS) by means of mesoporous Pd@Pt core–shell nanoparticles supported on MWCNT (Pd@Pt/MWCNT). The electrochemical behaviour of the drugs was assessed through cyclic voltammetry, while simultaneous determination was carried out using adsorptive stripping square wave voltammetry (AdSSWV). Under optimized conditions, the method exhibits linear responses towards simultaneous determination of DOX and DAS in the concentration ranges of 4.4–8580 nM and 38–9880 nM, with detection limits of 0.86 and 6.72 nM, respectively. Furthermore, the proposed platform was successfully used for reliable determination of DOX and DAS in urine and blood serum samples with good accuracy and precision. The satisfactory recoveries obtained in blood serum and urine samples showed the potential for application of the proposed platform in quality control in the pharmaceutical industry, clinical analysis and optimization of chemotherapeutic treatment. We found that the established sensor has several advantages in terms of high sensitivity and selectivity, ease of preparation, short analysis time, long-term stability and fast response.
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MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Tingting Li,Guoqiang Guo,Ting Zhang,Linfan Wang,Houwen Hu,Xinyu Luo,Xu Wang,Da Chen
It is of great significance to develop fluorescence sensors that are both high-performance and environmentally friendly for on-site monitoring of doxorubicin (DXR), which plays a crucial role in protecting the ecological environment and human health. In this work, a rapid and ultrasensitive fluorescence sensing strategy based on red beetroot-derived carbon dots (N-CDs) is proposed for the determination of DXR. N-CDs are successfully prepared through facile hydrothermal treatment using red beetroot as the sole raw material, which have a cyan emission at 496 nm under the 416 nm excitation. Further, the proposed N-CDs serve as a sensitive fluorescent probe for the ratiometric determination of DXR owing to the occurrence of fluorescence resonance energy transfer effect (FRET). The detection limit (LOD) of DXR is calculated as 78.3 nM within the good linear range of 3-35 μM. Simultaneously, to achieve precise on-site analysis, a real-time fluorescent assay platform is proposed, which combines the portability of 3D microfluidics paper-based analytical device (3D-µPAD) with the analysis capability of smartphone. This platform enables the real-time monitoring of DXR in real samples with acceptable recoveries (98.9 %-103.2 %), presenting the promising application for CDs in on-site detection and drug safety supervision.
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Biomaterials Research
·
2022
·Vol. 26
·期 1
·1-21
·
IF 15.863
Wu Hao,Wei Guoli,Luo Lixia,Li Lingchang,Gao Yibo,Tan Xiaobin,Wang Sen,Chang Haoxiao,Liu Yuxi,Wei Yingjie,Song Jie,Zhang Zhenhai,Huo Jiege
Background Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response.Methods In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological.Results Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment.Conclusion The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.
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RSC Advances
·
2016
·Vol. 6
·期 66
·61630-61640
·
IF 3.289
Lei Li,Beibei Lu,Qikui Fan,Jianning Wu,Lulu Wei,Jun Hou,Xuhong Guo,Zhiyong Liu
In this work, well-defined amphiphilic polyhedral oligomeric silsesquioxane (POSS) star-shaped inorganic/organic hybrid block copolymers with poly(ε-caprolactone)-poly(2-(dimethylamino)ethyl methacrylate)-co-poly(ethylene glycol) methacrylate (POSS-PCL-P(DMAEMA-co-PEGMA))16 were synthesized with different PCL segments via thiol-ene click reaction, ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP), which were confirmed by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). Subsequently, the polymers could self-assemble into micelles in aqueous solution, which were investigated by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-vis) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these triblock copolymers in water was investigated at different pH values of 5.0 and 7.4 for controlled doxorubicin release; the results indicated that the release rate of DOX could be effectively controlled by altering the pH and the release of drug loading efficiency (DLE) was up to 82% (w/w). Furthermore, CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the micelles had no associated cytotoxicity, possessed good biodegradability and biocompatibility, and identified the location of the DOX in HeLa cells. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action, and minimize the side effects of free DOX. Moreover, these flexible micelles with on-off switched drug release may offer a promising method to deliver a wide variety of hydrophobic payloads to tumor cells for cancer therapy.
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MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Shudi Yang,Zhaoxiang Ren,Mengtian Chen,Ying Wang,Bengang You,Weiliang Chen,Chenxi Qu,Yang Liu,Xuenong Zhang
In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4–siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox–siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Furthermore, the micelles loaded with TLR4–siRNA inhibited the migration and invasion of A549. Excellent tumor penetrating efficacy was also noted in the A549 tumor spheroids and solid tumor slices. In vivo, multiple results demonstrated the excellent tumor-targeting ability of AS1411-chitosan-ss-polyethylenimine-urocanic acid (ACPU) micelle in tumor tissues. The micelles exhibited excellent antitumor efficacy and low toxicity in the systemic circulation in lung-tumor-bearing BALB/c mice. These results conclusively demonstrated the great potential of the new graft copolymer micelle with targeting function for the targeted and efficient codelivery of chemotherapeutic drugs and genes in cancer treatment.
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DRUG DELIVERY
·
2020
·
IF 4.902
Yue Cao,Chao Wu,Ying Liu,Lili Hu,Wenjing Shang,Zhanshan Gao,Nan Xia
In this paper, we prepared doxorubicin-loaded folic acid-functionalized pH-sensitive photothermal therapy (PTT) traceable hollow mesoporous silica nanoparticles (DOX-HPCF) as a drug carrier for liver cancer treatment. According to TEM characterization, hollow mesoporous silica nanoparticles (HMSN) are monodispersed spherical particles with hollow structure. In vitro drug release experiments showed that HPCF exhibited pH-sensitive release. Cell uptake experiments showed that HPCF was successfully absorbed by SMMC-7721 cells. In addition, DOX-HPCF significantly inhibited the proliferation of SMMC-7721 cells, and the near-infrared (NIR) light group showed a more obvious inhibitory effect. In vivo anti-tumor experiments showed that DOX-HPCF-assisted PTT inhibited tumor growth significantly. Therefore, HPCF is a promising photothermotherapy carrier for the treatment of liver cancer.
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BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Gang Zheng,Meizhu Zheng,Ben Yang,Hui Fu,Yongqing Li
Breast cancer is the leading cause of cancer mortality in women worldwide. To overcome the toxic side effects and multidrug resistance (MDR) during doxorubicin (DOX) chemotherapy, an arginine-glycine-aspartic (RGD) tripeptide modified, pH-sensitive solid lipid nanoparticles (SLNs) is employed in this study. In this study, a RGD conjugated, pH sensitive lipid was synthesized using glycerin monostearate (GMS) and adipic acid dihydrazide (HZ) as lipid materials and named RGD-HZ-GMS. RGD-HZ-GMS was applied to encapsulate DOX to construct a RGD modified, DOX loaded SLNs (RGD-DOX-SLNs). To evaluate the anticancer effect of RGD-DOX-SLNs, breast cancer cell line (MCF-7 cells) and DOX resistant cell line (MCF-7/ADR cells) were used. in vivo tumor suspension and toxicity effects were evaluated on mice bearing MCF-7/ADR cells breast cancer model. RGD-DOX-SLNs had a uniformly spherical shape. The mean particle size and zeta potential of the RGD-DOX-SLNs was 96.3 nm and 35.6 mV, respectively. RGD-DOX-SLNs showed 5.58 fold higher area under the plasma concentration – time curve (AUC) compared with DOX solution. Terminal half life (T 1/2 ) and peak concentration (C max ) of RGD-DOX-SLNs was 10.85 h and 39.12 ± 2.71 L/kg/h. in vitro and in vivo antitumor results indicate that RGD-DOX-SLNs might be a promising novel lipid carrier which could improve breast cancer therapy.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2023
·
IF 4.9
Hui Jiang,Yingying Zhou,Dongdong Zheng,Yexiazi Cheng,Dacheng Xiang,Lixin Jiang,Jing Du
Triple negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and it is difficult to progress through traditional chemotherapy. Therefore, the treatment of TNBC urgently requires agents with effective diagnostic and therapeutic capabilities. In this study, we obtained programmed death-ligand 1 (PD-L1) antibody conjugated gold nanoshelled poly(lactic-co-glycolic acid) (PLGA) nanocapsules (NCs) encapsulating doxorubicin (DOX) (DOX@PLGA@Au-PD-L1 NCs). PLGA NCs encapsulating DOX were prepared by a modified single-emulsion oil-in-water (O/W) solvent evaporation method, and gold nanoshells were formed on the surface by gold seed growth method, which were coupled with PD-L1 antibodies by carbodiimide method. The fabricated DOX@PLGA@Au-PD-L1 NCs exhibited promising contrast enhancement in vitro ultrasound imaging. Furthermore, DOX encapsulated in NCs displayed good pH-responsive and photo-triggered drug release properties. After irradiating 200 μg/mL NCs solution with a laser for 10 min, the solution temperature increased by nearly 23°C, indicating that the NCs had good photothermal conversion ability. The targeting experiments confirmed that the NCs had specific target binding ability to TNBC cells overexpressing PD-L1 molecules. Cell experiments exhibited that the agent significantly reduced the survival rate of TNBC cells through photochemotherapy combination therapy. As a multifunctional diagnostic agent, DOX@PLGA@Au-PD-L1 NCs could be used for ultrasound targeted contrast imaging and photochemotherapy combination therapy of TNBC cells, providing a promising idea for early diagnosis and treatment of TNBC.
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