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Acid-sensitive PEGylated cabazitaxel prodrugs for antitumor therapy
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作者 Tao Liu Hui Zou +5 位作者 Jingqing Mu Na Yu Yang Xu Guohua Liu Xingjie Liang Shutao Guo 《Chinese Chemical Letters》 SCIE CAS CSCD 2021年第5期1751-1754,共4页
Although the antitumor drug cabazitaxel shows great therapeutic potential,its high toxicity and poor water solubility limit its utility.However,the use of stimuli-responsive prodrugs is a promising strategy for overco... Although the antitumor drug cabazitaxel shows great therapeutic potential,its high toxicity and poor water solubility limit its utility.However,the use of stimuli-responsive prodrugs is a promising strategy for overcoming these limitations.Herein,we report the synthesis of two highly water soluble,acidsensitive PEGylated acyclic-ketal-linked cabazitaxel prodrugs(PKCs)with improved antitumor efficacy.In an acidic tumor microenvironment,the PKCs hydrolyzed rapidly to release the native drug,whereas they were stable in the normal physiological environment.Compared with cabazitaxel injection,the PKCs had much higher maximum tolerated doses:and in an MDA-MB-231 subcutaneous xenograft nude mouse model,the PKCs showed better antitumor efficacy and safety than cabazitaxel injection.The prodrug strategy reported herein could be useful for the development of other water soluble,acidsensitive prodrugs with improved efficacy. 展开更多
关键词 PRODRUGS acid-sensitive Antitumor therapy CABAZITAXEL PEGYLATION
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pH-sensitive Nanoparticles for High Loading and Efficient Delivery of Doxorubicin 被引量:1
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作者 鲁孟丽 黄丽华 +7 位作者 ZHAN Siwen LI Juncan QIU Tong YANG Mengjia LI Jie TONG Miao ZHANG Xueqiong 施川 《Journal of Wuhan University of Technology(Materials Science)》 SCIE EI CAS CSCD 2023年第4期929-937,共9页
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-sensitiv... 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 DOXloaded 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. 展开更多
关键词 NANOPARTICLES acylhydrazone bond polymeric prodrug acid-sensitive
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Glycolysis in energy metabolism during seizures
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作者 Heng Yang Jiongxing Wu +4 位作者 Ren Guo Yufen Peng Wen Zheng Ding Liu Zhi Song 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第14期1316-1326,共11页
Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can partic... Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter Y-aminobutyric acid, and changes in the intra- and extracellular environment. 展开更多
关键词 neural regeneration REVIEWS epilepsy energy metabolism GLYCOLYSIS EPILEPTOGENESIS terminationATP aerobic metabolism 6-diphosphate kinase-1 N-methyI-D-aspartate receptor acid-sensitive1A ion channel y-aminobutyric acid intra- and extracellular environment voltage-gated Na+ andCa2+ adenosine receptors ATP receptor grants-supported paper NEUROREGENERATION
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PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA–docetaxel conjugates
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作者 Tao Liu Hui Zou +7 位作者 Jingqing Mu Xi Zhang Guohua Liu Na Yu Bo Yuan Xiaoyong Yuan Xingjie Liang Shutao Guo 《Chinese Chemical Letters》 SCIE CAS CSCD 2023年第9期225-229,共5页
Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs,but suffers from poor compatibility between drugs and nano... Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs,but suffers from poor compatibility between drugs and nanocarriers.Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines.However,the influence of hydrophobic length on the performance of this type of nanomedicine is little known.Here we synthesized two acid-sensitive ketal-linked mPEG-PDLLA–docetaxel prodrugs with different lengths of PDLLA,and engineered them into self-assembled sub-20 nm micellar nanomedicines for breast cancer chemotherapy.We found that the nanomedicine consisting of a mPEG-PDLLA–docetaxel prodrug with the shorter length of PDLLA stood out due to its potent cytotoxicity,deep penetration into multicellular spheroids,and improved in vivo anticancer performance.Additionally,our prodrug-based nanomedicines outperformed the generic formulation of commercial Nanoxel in terms of safety profile,tolerated doses,and tumor suppression.Our findings indicate that the hydrophobic content of a polymeric prodrug nanomedicine plays an important role in the performance of the nanomedicine,and should be instructive for developing polymeric prodrug-based nanomedicines with clinical translational potential. 展开更多
关键词 NANOMEDICINE PRODRUG DOCETAXEL mPEG-PDLLA acid-sensitive
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Facile preparation of acid/CO2 stimuli-responsive sheddable nanoparticles based on carboxymethylated chitosan
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作者 Weiwei FAN Jilu WANG +1 位作者 Jiajun FENG Yong WANG 《Frontiers of Materials Science》 SCIE CSCD 2019年第3期296-304,共9页
The present study describes the facile preparation of acid/CO2 stimuliresponsive sheddable nanoparticles based on carboxymethylated chitosan(CMCS).Commercially available CMCS was grafted with monomethoxy polyethylene ... The present study describes the facile preparation of acid/CO2 stimuliresponsive sheddable nanoparticles based on carboxymethylated chitosan(CMCS).Commercially available CMCS was grafted with monomethoxy polyethylene glycol(mPEG)chains via an acid/CO2 responsive linker,i.e.,benzoic-imine,and then was used for the cross-linking with CaCI2.With a high CMCS concentration up to 7 mg/mL,stable nanoparticles were successfully prepared.The particle size grew slightly with increasing the molecular weight of mPEG.When the concentration of CaCI2 and the feed ratio of CMCS to mPEG increased,the particle size decreased at first and then increased after reaching a minimum size.When the particles were stimulated by CO2 or acid,benzoic.imine cleaved quickly,and mPEG fell off the nanoparticles simultaneously,and then flocculation and precipitation occurred.These sheddable nanoparticles might have potential application in the biomedical field in eluding the intelligent drug delivery system. 展开更多
关键词 carboxymethylated CHITOSAN NANOPARTICLES benzoic-imine IONIC cross-linking acid-sensitivity
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