RSC Advances
·
2020
·Vol. 10
·期 44
·26059-26066
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IF 3.119
Shuwei Liu,Lu Wang,Bin Zhao,Ze Wang,Yinyu Wang,Bin Sun,Yi Liu
In clinical tumor therapy, traditional treatments such as surgery, radiotherapy and chemotherapy all have their own limitations. With the development of nanotechnology, new therapeutic methods based on nanomaterials such as photothermal therapy (PTT) have also emerged. PTT takes advantage of the poor thermal tolerance of tumor cells and uses the heat generated by photothermal reagents to kill tumor cells. A transition metal sulfide represented as Cu2S is an ideal photothermal reagent because of its easy preparation, high extinction coefficient and photothermal conversion efficiency. Surface modification of nanoparticles (NPs) is also necessary, which not only can reduce toxicity and improve colloidal stability, but also can provide the possibility of further chemotherapeutic drug loading. In this work, we report the fabrication of Tween-20 (Tw20)-modified and doxorubicin (Dox)-loaded Cu2S NPs (Cu2S/Dox@Tw20 NPs), which significantly improves the performance in tumor therapy. Apart from the enhancement of colloidal stability and biocompatibility, the drug loading rate of Dox in Tw20 reaches 11.3%. Because of the loading of Dox, Cu2S/Dox@Tw20 NPs exhibit chemotherapeutic behaviors and the tumor inhibition rate is 76.2%. Further combined with a near-infrared laser, the high temperature directly leads to the apoptosis of a large number of tumor cells, while the release of chemotherapeutic drugs under heat can not only continue to kill residual tumor cells, but also inhibit tumor recurrence. Therefore, with the combination of PTT and chemotherapy, the tumor was completely eliminated. Both hematological analysis and histopathological analysis proved that our experiments are safe.
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Oncotarget
·
2017
·
IF 5.168
Muhammad Sarfraz,Attia Afzal,Shahid Masood Raza,Sajid Bashir,Asadullah Madni,Muhammad Waseem Khan,Xiang Ma,Guangya Xiang
Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC). OA attenuated the cardiotoxicity induced by doxorubicin without compromising its anticancer activity. Apoptosis assays revealed that co-delivery of DOX and OA produced a synergistic anticancer effect. However, the drugs had antagonistic effects on cardiomyocytes. Female BALB/c nude mice treated with OA- and DOX-loaded liposomes (ODLs) exhibited reduced tumor growth, stable body weight, and stable organ indices. Reduced 20-HETE production suggested ODLs had limited cardiotoxicity. No changes in biochemical or histopathological markers were observed in mice treated with ODLs. Tailored co-delivery of OA and DOX may thus be an effective therapeutic strategy for treating HCC.
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International Journal of Nanomedicine
·
2017
·
IF 4.3
Yunfang Zhou,Shuanghu Wang,Xuhua Ying,Yifan Wang,Peiwu Geng,Aiping Deng,Zhihong Yu
Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy.
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Pharmacognosy Magazine
·
2025
·
IF 0.9
Qing Liu,Ying Lan,Zhe Bai
BackgroundHyperoside is a potential liver cell and mitochondrial protector, but there is no evidence to suggest that hyperoside can effectively treat doxorubicin (DOX) related liver toxicity.PurposeThis study aims to determine the role of hyperoside in DOX related liver toxicity and liver cell damage in vivo and in vitro.MethodsA mouse model of liver toxicity was induced by intraperitoneal injection of DOX, and hyperoside was administered orally for treatment. During this period, the weight and food intake of the mice were recorded. The morphology of mouse liver tissue was observed by hematoxylin and eosin staining. Oxidative stress and inflammatory status in mice were observed through serum inflammatory factors and liver oxidative stress markers. Mitochondrial damage is determined by the degree of mitochondrial DNA damage. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of pyroptosis and genes in the liver and liver cells.ResultsHyperoside can effectively treat DOX-induced oxidative stress and inflammatory status, liver function damage, and hepatocyte necrosis in mice. Further research suggests that the beneficial effect of hyperoside is achieved by inhibiting mitochondrial DNA damage in liver cells.ConclusionThis study indicates that hyperoside improves DOX-induced liver toxicity by inhibiting mitochondrial DNA damage.
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NEW JOURNAL OF CHEMISTRY
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2020
·Vol. 44
·期 29
·12633-12638
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IF 3.288
Weili Xue,Ashish Trital,Sihang Liu,Liangbo Xu
To simplify the preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu–Lys–Cys–Glu–Lys (EKCEK) were reacted with methacrylohydrazide (MAH) by click reaction, the product was further conjugated with doxorubicin (Dox) to form amphipathic molecules, and finally the amphipathic molecules self-assembled into doxorubicin-loaded micelles (EKCEK–Dox) in deionized water. TEM and DLS results showed that the EKCEK–Dox micelles were of the regular sphere, with the mean diameter approximately 70 nm. The drug-loading capacity of the prepared micelles was up to 44.6%, and the micelles were very stable in PBS solution. In vitro antitumor experiment showed that the EKCEK–Dox micelles had significant inhibition efficacy on MCF-7 cells, which was much better than the clinical antitumor drug (Doxil®). The IC50 of the EKCEK–Dox micelles (5.6 μg Dox equiv. per mL) was significantly lower than Doxil (8.9 μg Dox equiv. per mL). Therefore, the drug delivery system based on zwitterionic oligopeptides will be a promising strategy for cancer chemotherapy.
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ACS Biomaterials Science & Engineering
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2016
·
IF 0
Yike Fu,Xiaoyi Chen,Xiaozhou Mou,Zhaohui Ren,Xiang Li,Gaorong Han
Implantable localized drug delivery systems (LDDSs) have been intensively investigated for cancer therapy. However, the anticancer agent release behavior as well as the local therapeutic process in the complex physiological environment remains a dark zone and consequently hinders their clinical applications. Herein, a series of Er3+-doped electrospun strontium titanate (SrTiO3, STO) nanofibers with refined microstructural characteristics were exploited as a localized carrier for doxorubicin (DOX) delivery due to its light-responsive functionalities as well as expected biocompatibility. The highest DOX loading capacity and sustained releasing kinetics were obtained from the nanofibers with the highest surface area and lowest pore dimensions. Consequently, such nanofibers presented stronger in vitro anticancer efficacy to Hep G2 cells compared to that of other samples. More importantly, the amount of drug released was monitored by the ratio of green-to-red emission (I550/I660) due to the fluorescence resonance energy transfer (FRET) effect built between DOX molecules and upconversion photoluminescent nanofibers. The selective quenching effect of green emission due to DOX molecules was gradually weakened with drug releasing progress, whereas the intensity of red emission barely changed, resulting in an increased I550/I660 ratio. Such color evolution can be feasibly visualized by the naked eye. Monitoring with a spectral intensity ratio eliminates the disturbance of uncertainties in the complex physiological environment compared to just referring to the emission intensity. Such dual-color luminescent STO:Er nanofibers, designed based on the FRET mechanism, are therefore considered to be a promising new LDDS platform with ratiometric-monitored DOX release functionalities for future localized tumor therapeutic strategies.
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Journal of Macromolecular Science Part A-Pure and Applied Chemistry
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2021
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IF 2.168
Zhu Lin,Xiaomin Cheng
A novel amphiphilic polymer, carboxymethylated hydroxypropyl chitosan (HPCMS) was successfully synthesized for delivery of doxorubicin (DOX). The chemical structure and thermal stability were characterized by FTIR, 1H NMR and TGA, respectively. In aqueous medium, HPCMS could self-assembled into micelles with a low critical aggregation concentration of 0.54 mg/mL. The DOX-loaded HPCMS micelles showed a considerable drug-loading capacity of around 13 wt%. The prepared micelles were spherical morphology with average hydrodynamic diameter 300-380 nm and zeta potential of around −13 mv. The HPCMS/DOX micelles showed a sustained and pH-dependent drug release behavior in vitro and good stability. The drug release data could be well fitted with the Higuchi kinetic model, suggesting a diffusion-controlled mechanism. The diffusional exponent values indicated non-Fickian diffusion where the diffusion of drug and polymer relaxation had an important role in the process of drug release.
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JOURNAL OF MATERIALS SCIENCE
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2020
·Vol. 55
·期 22
·9525-9537
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IF 3.553
Bai Ting,Zhu Bobo,Du Zhaoyi,Shi Junling,Shao Dongyan,Kong Jie
The combination therapy by using two or more chemotherapeutic agents with different action mechanisms has shown to be an attractive strategy for cancer treatment with synergistic therapeutic effects, and also the side effects reduction by one agent replacing part of another one. In this work, an amphiphilic star copolymer with an H40 hyperbranched polyester as the core and poly(ε-caprolactone)-poly(2-dimethylaminoethylmethacrylate) copolymer incorporated with the fluorescent DTM groups as the arms were designed to encapsulate the model anti-cancer drug, doxorubicin (DOX), and a novel potential agent, avasimibe (Ava). Those two drugs could inhibit DNA replication and block acyl-CoA cholesterol acyltransferase-1 (ACAT-1) to induce the cell apoptosis, respectively. The model drugs could be easily loaded into the micelles with a high total drug-loading content toward 24.6% by altering the feeding drug ratios. Three molar ratios (DOX:Ava = 3:1, 1:1, and 1:3) of the drug-loaded micelles were prepared and evaluated for in vitro antitumor efficacy. Results showed that the micelles with 1:1 ratio exhibited the best synergistic cytotoxic activity against both K562 and HeLa cells. Furthermore, the dual-drug combination with efficient anticancer performance was also confirmed by live/dead staining, apoptosis, and cell cycle analysis. Moreover, the internalization of these dual-drug-loaded micelles could be monitored by fluorescent DTM groups and DOX. All these results suggested that the addition of Ava could cut down the dose of DOX to reduce its potential side effects and the co-delivery system could be a promising approach for an effective combination chemotherapy.
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Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Jianhong Liao,Haisheng Peng,Xuan Wei,Yajing Song,Can Liu,Dan Li,Yihua Yin,Xiong Xiong,Hua Zheng,Qun Wang
A novel bio-responsive co -delivery system based on Poly(DEA)-b-Poly(ABMA- co -OEGMA) (PDPAO, prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization) copolymers was constructed for enhanced cellular internalization and effective combination therapy. Reduction-sensitive 6-mercaptopurine (6MP) based prodrug and pH-sensitive doxorubicin (DOX) based prodrug were grafted onto PDPAO by an azide-alkyne “ Click Chemistry ” reaction to acquire a pH/reduction-sensitive polymeric prodrug (PDPAO@imine-DOX/ cis -6MP), which was able to self-aggregate to form polymeric micelles (M(DOX/6MP)) with an average particle size of 116 ± 2 nm in the water. The resultant micelles could maintain a stable sphere structure and show stability with a small particles' dispersion index in the blood. Importantly, it has been observed that the pH-sensitive surface charge-conversion accompanied pH-triggered DOX release in the biomimetic extracellular acidic environment of tumor tissue and a rapid dual-drug release triggered by pH and GSH in the intracellular environment. The in vitro evaluation of micelles on human cervical cancer (HeLa) and human promyelocytic leukemia (HL-60) cells showed an enhanced cellular uptake because of charge-conversion and exhibited a higher cell-killing performance. Moreover, the graft ratio of DOX and 6MP showed the ability to adjust the cytotoxicity; the micelles with a graft ratio of 2: 1 (M(DOX 2 /6MP)) displayed the higher cellular inhibition on either HeLa (combination index (CI) = 0.62) or HL-60 (CI = 0.35) cells. Overall, this novel dual-drug-conjugated delivery system might have important potential applications for combination therapy of cancer.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
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IF 3.65
Song Shen,Lin Wu,Jiejie Liu,Meng Xie,Haijun Shen,Xueyong Qi,Yongmin Yan,Yanru Ge,Yi Jin
To facilitate targeting drug delivery and combined therapy, we develop titanium dioxide-encapsulated Fe 3 O 4 nanoparticles (Fe 3 O 4 @TiO 2 NPs). Titanium dioxide (TiO 2 ), which is employed as a sonosensitizer for sonodynamic therapy (SDT), can also be used for the loading of doxorubicin (DOX). The fabricated Fe 3 O 4 @TiO 2 NPs exhibit pH-dependent loading and release of doxorubicin (DOX) in vitro. After incubation with cancer cells, reactive oxygen species (ROS) are generated efficiently upon the irradiation of ultrasound. In the biodistribution experiments, extremely high in vivo tumor accumulation of Fe 3 O 4 @TiO 2 NPs and long-time retention effect are observed. Compared with chemotherapy or sonodynamic treatment alone, the combined therapy demonstrated a synergistic effect, resulting in stronger cytotoxicity and higher therapeutic efficacy. Thus, the constructed NPs are endowed with multifunctions which allow them to selectively deliver combinatorial therapeutic payload to tumor with enhanced therapeutic effectiveness and minimal side effects.
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RSC Advances
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2022
·Vol. 12
·期 43
·27963-27969
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IF 4.036
Ling-Na Han,Kai-Qiang Wang,Zi-Ning Ren,Xue Yang,Xiao Duan,Sasirekha Krishnan,Abinaya Jaisankar,Jeong-Hui Park,Khandmaa Dashnyam,Wujie Zhang,José Luis Pedraz,Seeram Ramakrishna,Hae-Won Kim,Chang-Feng Li,Li-Hua Song,Murugan Ramalingam
In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics.
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Acta Biomaterialia
·
2018
·
IF 6.383
Doudou Hu,Ting Li,Zongpu Xu,Di Liu,Mingying Yang,Liangjun Zhu
A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, discounted tumor targetability, delivery efficacy and possible side effects limit the application in vascular delivery of NPs. Here we present water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) can resist the adsorption of serum proteins , preventing the formation of particle agglomerates. Following freeze-drying without addition of cryoprotectants, SSC@NPs powder can be easily resuspended into NP dispersion with a nearly monodispersed distribution. Additionally, SSC@NPs do not result in acute toxicity in mice at a dose of 400 mg/kg with a slow injection. Moreover, doxorubicin (DOX)-loaded SSC@NPs (DOX-SSC@NPs) diminish the biodistribution of DOX in the heart, mitigating DOX-induced cardiotoxicity of mice without compromising therapeutic efficacy. Our results suggest that the self-stabilized SSC@NPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents. Statement of Significance During manufacturing process such as freeze-drying, or interaction with complex fluids like blood, NPs for systemic drug delivery need to be highly dispersible and structurally intact. In this work, we have demonstrated the self-stability of SSC@NPs subjected to biological media and freeze-drying. This study represents the first work showing water-soluble SS could both act as a dispersion stabilizer and a cryoprotectant due to its hydrophilicity . Plus, good in vivo biocompatibility of SSC@NPs has been confirmed. Therefore, it may be promising that water-soluble SS can be generally used as a safe biomaterial against serum adsorption.
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