查找使用阿拉丁产品的科研文献

Self-assembly of polymer-doxorubicin conjugates to form polyprodrug micelles for pH/enzyme dual-responsive drug delivery

Mengna Zhang,Shujing Zhang,Kun Zhang,Zongyuan Zhu,Yalei Miao,Yudian Qiu,Panke Zhang,Xubo Zhao

Functionality of polymers is crucially fundamental to polymers. However, the application of polymers faces great challenges due to the insufficient function of hydrophobic chain, especially in drug delivery. One novel approach to solve this dilemma involves the use of medicated hydrophobic chains. Herein, the polymer-doxorubicin conjugates are synthesized from hydrophilic copolymer and hydrophobic chain composed of doxorubicin (DOX). DOX, a common hydrophobic anticancer drug , is used to serve as a hydrophobic pendant for inducing self-assembly of polymer-doxorubicin conjugates. The self-assembly of polymer-drug conjugates is employed to encapsulate the unreacted drug for the first time and form drug-loaded polyprodrug micelles that possess a low critical micelle concentration (CMC), which improves the use efficiency of expensive drug. The detachment of DOX moieties from polymer-doxorubicin conjugates caused by amidase facilitates the disintegration of DOX-loaded polyprodrug micelles to trigger the enhanced release of DOX in a slightly acidic medium. It is demonstrated that the DOX-loaded polyprodrug micelles have a higher suppression against cancer cells in in vitro investigations. This work thus proposes a strategy to modify the poor functionality of polymer-based nanostructures , through designing the medicated hydrophobic chains. This strategy facilitates the potential application of polymer-drug conjugates and provides profound insights into the effect of medicated polymer on drug delivery system.

A novel high doxorubicin-loaded Fe3O4@void@ZnO nanocomposite: pH-controlled drug release and targeted antitumor activity

Wang Chen,Wen Hao,Guo Hailing,Wang Xueyan,Shen Yuhua,Xie Anjian

A novel ferroferric oxide (Fe 3 O 4 )@void@zinc oxide (ZnO) nanocomposite was constructed through a template-assisted selective etching method. The experiment results showed that the magnetic saturation value of nanocomposite could reach to 44.07 emu g −1 , indicating the favorable magnetic targeting function. The presence of the void endowed the nanocomposite with high drug doxorubicin (DOX) loading capacity (85.65 μg mg −1 ). The pH-sensitive drug release was realized due to the gating effect of ZnO, and the DOX release rates were 92.7%, 60.8% and 23.4% at the pH values of 5.0, 6.5 and 7.4, respectively (37 °C). Besides, the Fe 3 O 4 @void@ZnO-DOX exhibited desirable antitumor effects attributed to their cellular uptake and above advantages. Therefore, the Fe 3 O 4 @void@ZnO nanocomposite may serve as a promising drug carrier in cancer therapy and other biomedical applications.

Mitochondrial targeted doxorubicin derivatives delivered by ROS-responsive nanocarriers to breast tumor for overcoming of multidrug resistance

Xin-Cheng Zhong,Ming-Han Shi,Hui-Na Liu,Jie-Jian Chen,Tian-Tian Wang,Meng-Ting Lin,Zhen-Tao Zhang,Yi Zhou,Yi-Ying Lu,Wen-Hong Xu,Jian-Qing Gao,Dong-Hang Xu,Min Han,Yi-Ding Chen

Carrier-free nanoassembly of doxorubicin prodrug and siRNA for combinationally inducing immunogenic cell death and reversing immunosuppression

Senbiao Chen,Dongdong Li,Xiaojiao Du,Xinyu He,Mengwen Huang,Yang Wang,Xianzhu Yang,Jun Wang

Doxorubicin (DOX) can elicit antitumor immunity responses by inducing immunogenic cell death (ICD) but also triggers upregulated expression of various immunosuppressive genes to counteract the ICD effect. To resolve this conflict, a carrier-free nanoassembly of acid-activatable DOX prodrug and small interfering RNA (siRNA) was developed to combinationally induce ICD and reverse immunosuppression. The carrier-free nanoassembly with rather high drug contents (4.13 % for siRNA and 21.67 % for DOX) was formed via cooperative π–π stacking and electrostatic interactions. The formed nanoassembly, termed as [email protected] :siRNA, possessed a well-defined nanostructure: a core consisting of DOX plus siRNA and a shell consisting of polyethylene glycol (PEG). It has been demonstrated that this carrier-free nanoassembly carrying siRNA targeting PD-L1 can significantly increase tumor-infiltrating T lymphocytes, improve interferon-γ (IFN-γ) expression, and ultimately strengthen the ICD effect of the DOX prodrug, resulting in a significantly enhanced anticancer immune response and superior tumor growth inhibition. In addition, carrier-free nanoassembly [email protected] :siRNA can also be conveniently extended as a general strategy to combine chemotherapy and immunotherapy, providing a facile avenue for improving cancer chemoimmunotherapy.

Doxorubicin-loaded pH-responsive nanoparticles coated with chlorin e6 for drug delivery and synergetic chemo-photodynamic therapy

Junlong Liang,Xiaokang Jin,Biling Chen,Jinhua Hu,Qianwei Huang,Junmin Wan,Zhiwen Hu,Bing Wang

The integration of chemotherapy drugs and photosensitizers to form versatile nanoplatforms for achieving chemo-photodynamic synergetic therapy has shown great superiority in tumor theranostic applications. We constructed pH-responsive nanoparticles (DOX/PB NPs) encapsulating the chemotherapeutic drug doxorubicin (DOX) into the cores of PLGA NPs coated with bovine serum albumin (BSA) via a water-in-oil (W/O/W) emulsion method. A simple and efficient chemo-photodynamic synergetic nanoplatform (DOX/PB@Ce6 NPs) was obtained by the adsorption of photosensitizer chlorin e6 (Ce6) onto the surface of the DOX/PB NPs. With optimal size, pH-responsive drug release behavior and excellent singlet oxygen production, the DOX/PB@Ce6 NPs have the potential to enhance anti-tumor efficiency. The cellular uptake, cytotoxicity, chemo-photodynamic synergetic effect and biocompatibility of the NPs were evaluated based on HeLa cells via in vitro experiments. The in vitro chemo-photodynamic synergetic experiments indicated that the DOX/PB@Ce6 NPs had remarkable cancer cell killing efficiency under laser irradiation. Notably, by hemolysis assay, all the NPs displayed excellent blood compatibility and were expected to be applicable for intravenous injection. In summary, the designed DOX/PB@Ce6 NPs multifunctional theranostic nanoplatform had excellent reactive oxygen species generation and would be a potential therapeutic platform for chemo-photodynamic synergetic therapy.

Doxorubicin-loading core-shell pectin nanocell: A novel nanovehicle for anticancer agent delivery with multidrug resistance reversal

Jiabi Ouyang,Mohui Yang,Tian Gong,Jinlai Ou,Yani Tan,Zhen Zhang,Sha Li

Tumor is a prevalent great threat to public health worldwide and multidrug resistance (MDR) of tumor is a leading cause of chemotherapy failure. Nanomedicine has shown prospects in overcoming the problem. Doxorubicin (DOX), a broad-spectrum anticancer drug, showed limited efficacy due to MDR. Herein, a doxorubicin containing pectin nanocell (DOX-PEC-NC) of core-shell structure, a pectin nanoparticle encapsulated with liposome-like membrane was developed. The DOX-PEC-NC, spheroid in shape and sized around 150 nm, exerted better sustained release behavior than doxorubicin loading pectin nanoparticle (DOX-PEC-NP) or liposome (DOX-LIP). In vitro anticancer study showed marked accumulation of doxorubicin in different tumor cells as well as reversal of MDR in HepG2/ADR cells and MCF-7/ADR cells caused by treatment of DOX-PEC-NC. In H 22 tumor-bearing mice, DOX-PEC-NC showed higher anticancer efficacy and lower toxicity than doxorubicin. DOX-PEC-NC can improve anticancer activity and reduce side effect of doxorubicin due to increased intracellular accumulation and reversal of MDR in tumor cells, which may be a promising nanoscale drug delivery vehicle for chemotherapeutic agents.

Co-delivery of chlorin e6 and doxorubicin using PEGylated hollow nanocapsules for ‘all-in-one’ tumor theranostics

Qian Li,Mengmeng Hou,Junjie Ren,Shiyu Lu,Zhigang Xu,Chang Ming Li,Yuejun Kang,Peng Xue

Aim: Hollow mesoporous copper sulfide nanocapsules conjugated with poly(ethylene glycol) (PEG), doxorubicin and chlorin e6 (HPDC) were synthesized for fluorescence imaging and multimodal tumor therapy. Materials & methods: HPDC were synthesized by encapsulating chlorin e6 and doxorubicin into PEGylated nanocapsules via a simple precipitation method. The photothermal/photodynamic effects, drug release, cellular uptake, imaging capacities and antitumor effects of the HPDCs were evaluated. Results: This smart nanoplatform is stimulus-responsive toward an acidic microenvironment and near infrared laser irradiation. Moreover, fluorescence imaging-guided and combined photothermal/photodynamic/chemotherapies of tumors were promoted under laser activation and led to efficient tumor ablation, as evidenced by exploring animal models in vivo. Conclusion: HPDCs are expected to serve as potent and reliable nanoagents for achieving superior therapeutic outcomes in cancer management.

Co-Delivery of Metformin Enhances the Antimultidrug Resistant Tumor Effect of Doxorubicin by Improving Hypoxic Tumor Microenvironment

Ying Li,Jing Luo,Meng-Ting Lin,Pei Zhi,Wang-Wei Guo,Min Han,Jian You,Jian-Qing Gao

Doxorubicin (DOX) is a first-line chemo drug for cancer therapy, yet it fails to treat multi-drug-resistant tumors. Hypoxia is a major causative factor leading to chemotherapy failure. Particularly, hypoxia up-regulates its responsive transcription factor—hypoxia-inducible factors (HIF)—to induce the overexpression of drug resistant genes. Metformin (MET) is recently found to cooperate with DOX against multiple tumors. As a mitochondrial inhibitor, MET could suppress tumor oxygen consumption, and thereby modulate the hypoxic tumor microenvironment. In this study, we used cationic liposomes to codeliver both DOX and MET for treating multi-drug-resistant breast cancer cells—MCF7/ADR. Faster release of MET enhanced the cytotoxicity of DOX through attenuating hypoxic stress both in vivo and in vitro. MET diminished the cellular oxygen consumption and inhibited HIF1α and P-glycoprotein (Pgp) expression in vitro. In addition, the dual-drug-loaded liposomes increased tumor targeting and intratumoral blood oxygen saturation, which suggested that the tumor reoxygenation effect of MET facilitated the exertion of its synergistic activity with DOX against MCF7/ADR xenografts. In general, our study represents a feasible strategy to boost the therapeutic effect in treating multi-drug-resistant cancer by improving the hypoxic tumor microenvironment.

PVA reinforced gossypolone and doxorubicin π–π stacking nanoparticles towards tumor targeting and ultralow dose synergistic chemotherapy

Yiming Liu,Ke Li,Youshen Wu,Jingwen Ma,Peng Tang,Yongchun Liu,Daocheng Wu

To improve the tumor synergistic therapeutic effects of carrier-free dual-drug delivery systems and realize ultralow dose administration, we developed a tumor targeting and high-efficiency synergistic chemotherapy system (HA-Gn@DPGn NPs) based on polyvinyl alcohol (PVA) reinforced gossypolone (Gn) and doxorubicin (DOX) π–π stacking nanoparticles (DPGn NPs), in which PVA filled the gaps between Gn and DOX and bridged Gn and DOX tightly. Hyaluronic acid modifier hyaluronic acid-gossypolone (HA-Gn) was covered on the surface of DPGn NPs to form HA-Gn@DPGn NPs that procured active targeting properties. This system presented a spherical shape with a uniform hydrodynamic size of 87 ± 6.8 nm, a high drug loading of 80.31%, and high stability. FTIR and UV spectra demonstrated that HA-Gn was covered on the surface of the system and showed significant π–π stacking properties. A considerably low combination index of Gn and DOX (0.1862) was determined at an ultra-low dose of DOX under a Gn : DOX ratio of 50 : 1. HA-Gn@DPGn NPs also demonstrated excellent tumor synergistic therapeutic efficacy (TIR > 87%) at an ultralow dose of DOX and Gn. This system demonstrates high tumor comprehensive synergistic therapeutic efficacy at an ultralow drug dose with multiple favorable therapeutic characteristics, including negligible side effects, tumor targeting ability and thermal-responsive drug release, and thus has considerable potential for tumor synergistic therapy.

Folate-conjugated and pH-triggered doxorubicin and paclitaxel co-delivery micellar system for targeted anticancer drug delivery

Lijing Niu,Feiyan Zhu,Bowen Li,Lingling Zhao,Hongze Liang,Yinghua Yan,Hui Tan

A folate-conjugated and pH-sensitive polymeric micellar system for the co-delivery of DOX and PTX was studied. A doxorubicin conjugated prodrug was synthesized via Schiff's base reaction. Subsequently, folate was grafted onto the prodrug and PTX was encapsulated. Sustained drug release of both DOX and PTX from the polymeric micelles was observed and the release rate could be accelerated by decreasing the media pH. A cellular uptake assay revealed that the polymeric micelles were internalized in the cytoplasm via endocytosis by SW1353 cells, and the cellular uptake was enhanced for the folate-conjugated micelles due to an active FR-mediated endocytosis pathway, showing stronger red fluorescence compared to that of non-folate micelles. The in vitro anticancer efficiency of the polymeric micellar system was evaluated using a cytotoxicity assay by incubating different drug formulations with the SW1353 cells. Both free drugs and micellar formulations displayed inhibition of cell growth at different levels, while the folate-conjugated dual-drug loaded polymeric micelles (Folate–Oxd–DOX/PTX) displayed a much lower IC50 value than other drug formulations, indicating a desirable in vitro anticancer efficiency due to the synergistic effect of co-delivery and active targeting. Thus, the polymeric micellar system is a promising platform for targeted cancer chemotherapy.

Ursolic acid prevents doxorubicin-induced cardiac toxicity in mice through eNOS activation and inhibition of eNOS uncoupling

Haiman Mu,Haiwen Liu,Jiayi Zhang,Jianhua Huang,Chen Zhu,Yue Lu,Yueping Shi,Yi Wang

In addition to the known antitumour effects of ursolic acid (UA), increasing evidence indicates that this molecule plays a role in cardiac protection. In this study, the effects of ursolic acid on the heart in mice treated with doxorubicin (DOX) were assessed. The results showed that ursolic acid improved left ventrical fractional shortening (LVFS) and left ventrical ejection fraction (LVEF) of the heart, increased nitrogen oxide (NO) levels, inhibited reactive oxygen species (ROS) production and decreased cardiac apoptosis in mice treated with doxorubicin. Mechanistically, ursolic acid increased AKT and endothelial nitric-oxide synthase (eNOS) phosphorylation levels, and enhanced eNOS expression, while inhibiting doxorubicin induced eNOS uncoupling through NADPH oxidase 4 (NOX4) down-regulation. These effects of ursolic acid resulted in heart protection from doxorubicin-induced injury. Therefore, ursolic acid may be considered a potential therapeutic agent for doxorubicin-associated cardiac toxicity in clinical practice.

Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice

Zhi-Meng Xu,Cheng-Bin Li,Qing-Ling Liu,Ping Li,Hua Yang

Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.Keywords:ginsenoside Rg1;doxorubicin;cardiotoxicity;autophagy;endoplasmic reticulum stress