Frontiers in Pharmacology
·
2022
·
IF 5.988
Qin Yeyu,Xie Jing,Zheng Ruihe,Li Yuhang,Wang Haixia
Doxorubicin (DOX) is one of the most common chemotherapeutic anti-cancer drugs. However, its clinical use is restricted by serious cardiotoxicity. Oleoylethanolamide (OEA), a structural congener of endocannabinoid anandamide, is the endogenous agonist of peroxisome proliferator activated-receptor α (PPARα) and transient receptor potential cation channel vanilloid-1 (TRPV1), and involved in many physiological processes. The present study aimed to determine whether OEA treatment protects against DOX-induced cytotoxicity (DIC) and gain insights into the underlying mechanism that mediate these effects. Our data revealed that Oleoylethanolamide treatment improved the myocardial structure in DOX-challenged mice by attenuating cardiac oxidative stress and cell apoptosis. OEA also alleviated DOX-induced oxidative stress and apoptosis dysregulation in HL-1 cardiomyocyte. These effects were mediated by activation of TRPV1 and upregulation of PI3K/ Akt signaling pathway. Inhibition of TRPV1 and PI3K reversed the protective effects of OEA. Taken together, our data suggested that OEA protects against DIC through a TRPV1- mediated PI3K/ Akt pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
·
2023
·Vol. 38
·期 4
·929-937
·
IF 1.6
Lu Mengli,Huang Lihua,Zhan Siwen,Li Juncan,Qiu Tong,Yang Mengjia,Li Jie,Tong Miao,Zhang Xueqiong,Shi Chuan
An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin. Doxorubicin(DOX) was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction, then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs, and nanoparticles were formed through self-assembling. Moreover, the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry (UV), nuclear magnetic resonance spectroscopy ( 1 H-NMR), fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The mean diameter of the self-assembled nanoparticles is 165 nm, while the morphology is a relatively uniform spherical shape. Moreover, these DOX-loaded nanoparticles showed pH-triggered drug release behavior. Compared with free DOX, CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells. The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.
✓ 已验证
产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2020
·
IF 7.097
Jiang Yu,Yingli Wang,Shuang Zhou,Jinbo Li,Jiamei Wang,Dongxu Chi,Xue Wang,Guimei Lin,Zhonggui He,Yongjun Wang
The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX- S -DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu 2+ ) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu 2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials
·
2019
·Vol. 12
·期 5
·766
·
IF 2.972
Yan Li,Fangxiang Song,Liang Cheng,Jin Qian,Qianlin Chen
Large-pore coralline mesoporous silica microparticles (CMS) were synthesized using the triblock polymer PEG-b-PEO-b-PEG and a hydrothermal method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the coralline morphology of the fabricated materials. The Brunauer–Emmett–Teller (BET) method and the Barrett–Joyner–Halenda (BJH) model confirmed the existence of large pores (20 nm) and of a tremendous specific surface area (663.865 m2·g−1) and pore volume (0.365 cm3·g−1). A novel pH-sensitive multiamine-chain carboxyl-functionalized coralline mesoporous silica material (CMS–(NH)3–COOH) was obtained via a facile “grafting-to” approach. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) validated the effective interfacial functionalization of CMS with carboxyl and multiamine chains. The encapsulation and release behavior of the dual drug (gefitinib (GB) and doxorubicin (DOX)) was also investigated. It was found that CMS–(NH)3–COOH allows rapid encapsulation with a high loading capacity of 47.36% for GB and 26.74% for DOX. Furthermore, the release profiles reveal that CMS–(NH)3–COOH can preferably control the release of DOX and GB. The accumulative release rates of DOX and GB were 32.03% and 13.66%, respectively, at a low pH (pH 5.0), while they reduced to 8.45% and 4.83% at pH 7.4. Moreover, all of the modified silica nanoparticles exhibited a high biocompatibility with a low cytotoxicity. In particular, the cytotoxicity of both of these two drugs was remarkably reduced after being encapsulated. CMS–(NH)3–COOH@GB@DOX showed tremendously synergistic effects of the dual drug in the antiproliferation and apoptosis of A549 human cancer cells in vitro.Keywords:mesoporous silica;multiamine chains;carboxylation;interfacial functionalization;great synergistic effects
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Lingwei Meng,Xiaoyang Chu,Haoyue Xing,Xuan Liu,Xin Xin,Liqing Chen,Mingji Jin,Youyan Guan,Wei Huang,Zhonggao Gao
Glioblastoma is a grade IV malignant glioma with high recurrence and metastasis and faces a therapeutic obstacle that the blood-brain barrier (BBB) severely hinders the brain entry and efficacy of therapeutic drugs. Previous studies suggest that borneol (BO) has been used to enhance interested drugs to penetrate the BBB. In this study, a borneol-modified nanomicelle delivery system was established to facilitate the brain entry of doxorubicin for glioblastoma therapy. Herein, we firstly conjugated borneol molecules with DSPE-PEG 2000 -COOH to synthesize a novel carrier DSPE-PEG 2000 -BO and also characterized its structure. Doxorubicin-loaded nanomicelles (DOX BO-PMs) were prepared using DSPE-PEG 2000 -BO via electrostatic interaction and the physicochemical properties were investigated. The average particle size and zeta potential of DOX BO-PMs were respectively (14.95 ± 0.17)nm and (−1.27 ± 0.06)mV, and the drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 ± 0.49)% and (14.62 ± 0.39)%, respectively. The drug release of the DOX BO-PMs exhibited a both time- and pH-dependent pattern. The results demonstrated that DOX BO-PMs significantly enhanced the transport efficiency of DOX across the BBB and also exhibited a quick accumulation in the brain tissues. The in vitro anti-proliferation assay results suggested that DOX BO-PMs exerted a strong inhibitory effect on proliferation of glioblastoma cells. Importantly, in vivo antitumor results demonstrated that DOX BO-PMs significantly inhibited the tumor growth and metastasis of glioblastoma. In conclusion, DOX BO-PMs can improve the glioblastoma therapeutic outcomes and become a promising nanodrug candidate for the application of doxorubicin in the field of glioblastoma therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Micro & Nano Letters
·
2019
·Vol. 14
·期 5
·520-525
·
IF 0.975
Tingting Zhang,Kun Zhang,Feng Jiang,Jianfeng Zhang,Xin Song,Jinshun Zhao
Development of stimuli-responsive nanocomposites for the delivery anticancer drug has attracted considerable attention. A magnetic/pH dual-responsive nanocomposite was synthesised by amide condensation reaction and developed for cancer therapy. The PEGylated citric-coated Fe 3 O 4 (PCI)–graphene oxide (GO) nanocomposites was constructed by a three-step process. Fe 3 O 4 magnetic nanoparticles were firstly coated with citric acid, and then covalently linked to aminated polyethylene glycol (NH 2 –PEG–NH 2 ); lastly, the PCI was covalently conjugated to graphite oxide to obtain PCI–GO nanocomposites. The PCI–GO nanocomposites were characterised by X-ray diffraction, scanning electron microscopy, Fourier transform-infrared, ultraviolet–visible, and thermogravimetry. The magnetic of nanocomposites was confirmed by a vibrating sample magnetometer. Due to the hydrogen bond, π – π stacking and electrostatic interaction between the doxorubicin (DOX) hydrochloride and PCI–GO nanocomposites, the PCI–GO nanocomposites could load DOX effectively and with a high drug loading content (about 87.6%). The DOX-loaded PCI–GO (DOX/PCI–GO) nanocomposites exhibited pH-responsive release behaviour. The DOX/PCI–GO nanocomposites could effectively inhibit tumour growth in vitro, which was comparable to the antitumour effect of free DOX. The result indicates that the PCI–GO nanocomposites exhibit great potential for a magnetic targeted drug delivery system in multimodal and synergistic cancer therapy.
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Yan Wang,Shurong Ma,Zhongshi Xie,Haishan Zhang
Doxorubicin was chemically conjugated to a biodegradable polymeric carrier as a polymer-doxorubicin (polymer-Dox) conjugate via an acid labile Schiff-base bond. Then, paclitaxel was physically encapsulated by the polymer-Dox conjugate to self assemble in water as micellar nanoparticles with both doxorubicin and paclitaxel in one nanoparticle. In this way, doxorubicin and paclitaxel were combined. The preparation of the polymer-doxorubicin conjugates, encapsulation of paclitaxel, characterization of nanoparticles was systematically studied and the biological evaluation of the free drug combination as well as the micellar platform combination in vitro was thoroughly detailed.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 16
·3297-3305
·
IF 4.726
Haibo Wang,Xiangsheng Liu,Yin Wang,Yangjun Chen,Qiao Jin,Jian Ji
Ideal drug delivery systems should have prolonged circulation in blood, high accumulation in tumors with fast cellular uptake and burst drug release in cancer cells. Herein, a pH-sensitive small-molecule phospholipid prodrug based on phosphorylcholine (PC) was designed to overcome these challenges. The prodrug was synthesized by conjugating doxorubicin (DOX) to 11-mercaptoundecyl phosphorylcholine via an acid-labile hydrazone linker (UnPC-hyd-DOX). This phospholipid prodrug can self-assemble into core–shell micelles with exact and very high drug loading content (56.2%). Interestingly, the PC prodrug micelles can strongly minimize nonspecific phagocytosis by macrophages. They exhibited better ability to be internalized by cancer cells than that of the PEG prodrug micelles, which indicated that the PC shell facilitated cancer cell internalization. Moreover, in vitro results further demonstrated that DOX of phospholipid prodrug micelles can effectively escape from endo/lysosomes to the cytosol and enter the nucleus. An in vivo study demonstrated that these PC prodrug micelles exhibited much lower cardiotoxicity than free DOX. Importantly, PC prodrug micelles showed significantly slower blood clearance than PEG prodrug micelles and free DOX.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2015
·Vol. 4
·期 3
·412-417
·
IF 3.831
Chao Chen,Pan Zheng,Ziyang Cao,Yinchu Ma,Jie Li,Haisheng Qian,Wei Tao,Xianzhu Yang
Redox-responsive polymers exhibit great potential as drug delivery systems. Herein, a redox-responsive PEGylated hyperbranched polyphosphoester (PPE) was synthesized through (A2 + B3) type polycondensation. The obtained hyperbranched PPE can self-assemble into nanoparticles in water. The biocompatibility of the nanoparticles was evaluated. The hydrophobic chemotherapy drug doxorubicin (DOX) can be efficiently encapsulated into the obtained nanoparticles. Such DOX-loaded nanoparticles exhibited excellent stability due to the PEGylation, and showed redox-responsive drug release behavior. In addition, flow cytometric analyses demonstrated that the redox-responsive nanoparticles could be efficiently internalized into the human breast cancer cell line MDA-MB-231, and intracellular glutathione enhanced the intracellular drug release from the redox-responsive hyperbranched PPE based nanoparticles. Therefore, such nanoparticles resulted in the enhanced inhibition of tumor cell growth, suggesting the potential of redox-responsive PEGylated hyperbranched PPE in anticancer drug delivery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 59
·47629-47639
·
IF 3.84
Lan Bai,Fei Song,Xiao-hui Wang,Jiang-yong-quan Cao,Xue Han,Xiu-li Wang,Yu-zhong Wang
In the field of anticancer drug delivery, improving drug loading capacity of carriers and achieving efficient intracellular drug transportation simultaneously is very difficult but they are important issues for the development of chemotherapy. Herein, a reversible ligand–metal-drug coordination architecture responsive to pH was employed to construct a smart drug delivery system, in which the ligand and metal can be regarded as a harbor and an anchor to not only moor the drug (doxorubicin, DOX) but also send the cargo precisely on time. Based on the strategy, DOX loading content of the system could run up to 26.1%. Owing to the stability of coordination bonds at neutral conditions, premature drug leakage was extremely suppressed to lower than 5%, while an almost complete drug release was realized at pH 5.0 as a result of breakage of the bonds. Presence of the coordination interaction played a key role in controlled release of DOX, which followed the first-order kinetics model in the case of non-coordinated systems but the pseudo-second-order kinetics model in the case of coordinated systems. Moreover, the metal-coordinated system could effectively take DOX into HeLa cells, presenting a comparable cancer therapy effect to free DOX. This study established exploitation of coordination interaction to connect drugs and carriers as a promising way to meet urgent needs for chemotherapy.
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Qian Zhu,Lixin Jia,Zhongfei Gao,Chunming Wang,Haoyang Jiang,Junfeng Zhang,Lei Dong
Doxorubicin (DOX) is a potent cancer chemotherapeutic agent, but its clinical use is severely limited by potentially lethal cardiotoxicity. Delivery of DOX by particulate carriers can be an effective way to reduce its distribution in cardiac tissue. In the present study, we developed a self-assembled, tumor-microenvironment-responsive delivery system for DOX. The core of the carrier was built upon the DOX/DNA intercalation, which was further combined with cationic gelatin (C-gel) to form the complex GDD. GDD was then packaged into a complex, namely, HDD, based on the electrostatic interactions between the positively charged C-gel and negatively charged human serum albumin (HSA). The HSA molecules on the surface of the complex HDD effectively helped the particle evade the filtration of the body when injected into the circulation and passively accumulate into the tumor sites. After entering the tumor tissue, where albumin is rapidly consumed, GDD was release from HDD and the C-gel was then digested by the tumor-specific matrix metalloproteinase (MMPs) to free the DOX/DNA intercalation. Deoxyribonucleases (DNases) in the tissue could completely destroy the DNA molecules to release DOX into the microenvironments. After a series of in vitro optimization tests, we evaluated the anticancer capacity and cardiac toxicity of HDD in two animal models with cancer. The results suggested that HDD had a higher anticancer efficacy and a significantly lower cardiotoxicity than free DOX. Additionally, the main components of the carrier are all clinically approved materials. Taken together, our present delivery system is safe and efficient and has high potential for further clinical trials.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2013
·Vol. 3
·期 2
·261-272
·
IF 0
Chun-Yang Sun,Shuang Dou,Jin-Zhi Du,Xian-Zhu Yang,Ya-Ping Li,Jun Wang
Polyphosphoesters with repeating phosphoester linkages in the backbone can be easily functionalized, are biodegradable and potentially biocompatible, and may be potential candidates as polymer carriers of drug conjugates. Here, the efficacy of a polyphosphoester drug conjugate as an anticancer agent in vivo is assessed for the first time. With controlled synthesis, doxorubicin conjugated to poly(ethylene glycol)- block -polyphosphoester (PPEH–DOX) via labile hydrazone bonds form spherical nanoparticles in aqueous solution with an average diameter of ≈60 nm. These nanoparticles are effectively internalized by MDA-MB-231 breast cancer cells and release the conjugated doxorubicin in response to the intracellular pH of endosomes and lysosomes, resulting in significant antiproliferative activity in cancer cells. Compared with free doxorubicin injection, PPEH–DOX injection exhibits much longer circulation behavior in the plasma of mice and leads to enhanced drug accumulation in tumor cells. In an MDA-MB-231 xenograft murine model, inhibition of tumor growth with systemic delivery of PPEH–DOX nanoparticles is more pronounced compared with free doxorubicin injection, suggesting the potential of polyphosphoesters as carriers of drug conjugates in cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
危险品化学品经营许可证（带存储）