The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native de...The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey,which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment.In this review,we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy,including optimizing the intrinsic physicochemical properties and external modification.Finally,the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented.We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.展开更多
Increasing intracellular drug concentration is an effec-tive way for cancer chemotherapeutics to enhance efficacy and combat drug resistance.In this work,a series of anticancer drug conjugates were prepared by linking...Increasing intracellular drug concentration is an effec-tive way for cancer chemotherapeutics to enhance efficacy and combat drug resistance.In this work,a series of anticancer drug conjugates were prepared by linking thiol-modified oligo(p-phenylene viny-lene)with paclitaxel,vincristine,teniposide,tamoxi-fen,doxorubicin,or podophyllotoxin(OPV-S-Drugs)through a Michael addition reaction.展开更多
Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene a...Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms.展开更多
The drug metabolism is a biochemical process on modification of pharmaceutical substances through specialized enzymatic systems. Changes in the expression of drug-metabolizing enzyme genes can affect drug metabolism. ...The drug metabolism is a biochemical process on modification of pharmaceutical substances through specialized enzymatic systems. Changes in the expression of drug-metabolizing enzyme genes can affect drug metabolism. Recently, epigenetic regulation of drug-metabolizing enzyme genes has emerged as an important mechanism. Epigenetic regulation refers to heritable factors of genomic modifications that do not involve changes in DNA sequence. Examples of such modifications include DNA methylation, histone modifications, and non-coding RNAs. This review examines the widespread effect of epigenetic regulations on genes involved in drug metabolism, and also suggests a network perspective of epigenetic regulation. The epigenetic mechanisms have important clinical implications and may provide insights into effective drug development and improve safety of drug therapy.展开更多
Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for...Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".展开更多
The feature of the surface coating can affect important properties of iron oxide nanoparticles(IONPs), it is therefore critical for further understanding how these materials react to physiological conditions, which is...The feature of the surface coating can affect important properties of iron oxide nanoparticles(IONPs), it is therefore critical for further understanding how these materials react to physiological conditions, which is still needed to fully exploit the potential of IONPs for their theranostic applications. In this work, we prepared IONPs which surface were modified with citric acid(CA), chitosan(CS) and folic acid conjugated chitosan(FA-g-CS). respectively. Their physicochemical properties were investigated using FT-IR, TEM,powder XRD, VSM, TGA, DLS and zeta potential. We found that CA-IONP dispersion was composed of monocrystalline particles while CS-IONP and FA-g-CS-IONP were composed of polycrystalline aggregates. All IONPs retained the crystalline structure of magnetite and exhibited the superparamagnetic behavior. Their saturation magnetization decreased with the increase in the amount of their organic coatings. Their drug loading capacities, drug release patterns and in vitro anticancer efficiencies were studied by using doxorubicin(DOX) as a model drug. DOX@CS-IONP and DOX@FA-g-CSIONP exhibited lower drug loading while showing higher water dispersity when compared with DOX@CA-IONP. All IONPs were surface charged and they tended to agglomerate in medium with high pH value and ionic strength. In the presence of chitosan or FA-g-CS coatings, their DOX release rate was slowed down compared with that of DOX@CA-IONP. Unloaded IONPs exhibited nearly no cytotoxicity on both cancer cells and normal cells in the presence of chitosan and FA-g-CS when compared with CA-IONP which presented high cytotoxicity. However, DOX@FA-g-CS-IONP showed significantly cytotoxicity on folate receptors(FRs) positive breast cancer cells while exhibiting nearly no cytotoxicity on FRs negative normal cells. Results presented in this study were valuable to the design and fabrication of IONPs-based system for better theranostic applications.展开更多
基金supported by grants from the National Key Research and Development Program of China(No.2018YFC1106103)the National Natural Science Foundation of China(Grant No.51973135).
文摘The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey,which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment.In this review,we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy,including optimizing the intrinsic physicochemical properties and external modification.Finally,the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented.We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.
基金The authors are grateful to the National Natural Sci-ence Foundation of China(Nos.21473221,91527306,and 21661132006)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16020804)the Youth Innovation Promotion Association Chinese Academy of Sciences(No.2016029).
文摘Increasing intracellular drug concentration is an effec-tive way for cancer chemotherapeutics to enhance efficacy and combat drug resistance.In this work,a series of anticancer drug conjugates were prepared by linking thiol-modified oligo(p-phenylene viny-lene)with paclitaxel,vincristine,teniposide,tamoxi-fen,doxorubicin,or podophyllotoxin(OPV-S-Drugs)through a Michael addition reaction.
基金Supported by Natural Science Foundation of Hubei Province,No.2016CFB596Wuhan City Medical Research Project,Nos.WX15B14and WX17Q39Hubei Province Scientific Research Project,No.WJ2015MB137
文摘Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms.
基金supported by the National Institute of Health,National Institute of General Medical Sciences (No.R01GM087376)National Institute of Health,National Institute for Environmental Health Sciences (No.R01ES-019487)
文摘The drug metabolism is a biochemical process on modification of pharmaceutical substances through specialized enzymatic systems. Changes in the expression of drug-metabolizing enzyme genes can affect drug metabolism. Recently, epigenetic regulation of drug-metabolizing enzyme genes has emerged as an important mechanism. Epigenetic regulation refers to heritable factors of genomic modifications that do not involve changes in DNA sequence. Examples of such modifications include DNA methylation, histone modifications, and non-coding RNAs. This review examines the widespread effect of epigenetic regulations on genes involved in drug metabolism, and also suggests a network perspective of epigenetic regulation. The epigenetic mechanisms have important clinical implications and may provide insights into effective drug development and improve safety of drug therapy.
文摘Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
基金supported by the State Key Basic Research Program of the PRC(No.2014CB744501)the National Key Research and Development Program of China(No.2017YFA0205301)+1 种基金the National Natural Science Foundation of China(Nos.61527806,61471168 and 61871180)Open Funding of State Key Laboratory of Oral Diseases(No.SKLOD2018OF02)
文摘The feature of the surface coating can affect important properties of iron oxide nanoparticles(IONPs), it is therefore critical for further understanding how these materials react to physiological conditions, which is still needed to fully exploit the potential of IONPs for their theranostic applications. In this work, we prepared IONPs which surface were modified with citric acid(CA), chitosan(CS) and folic acid conjugated chitosan(FA-g-CS). respectively. Their physicochemical properties were investigated using FT-IR, TEM,powder XRD, VSM, TGA, DLS and zeta potential. We found that CA-IONP dispersion was composed of monocrystalline particles while CS-IONP and FA-g-CS-IONP were composed of polycrystalline aggregates. All IONPs retained the crystalline structure of magnetite and exhibited the superparamagnetic behavior. Their saturation magnetization decreased with the increase in the amount of their organic coatings. Their drug loading capacities, drug release patterns and in vitro anticancer efficiencies were studied by using doxorubicin(DOX) as a model drug. DOX@CS-IONP and DOX@FA-g-CSIONP exhibited lower drug loading while showing higher water dispersity when compared with DOX@CA-IONP. All IONPs were surface charged and they tended to agglomerate in medium with high pH value and ionic strength. In the presence of chitosan or FA-g-CS coatings, their DOX release rate was slowed down compared with that of DOX@CA-IONP. Unloaded IONPs exhibited nearly no cytotoxicity on both cancer cells and normal cells in the presence of chitosan and FA-g-CS when compared with CA-IONP which presented high cytotoxicity. However, DOX@FA-g-CS-IONP showed significantly cytotoxicity on folate receptors(FRs) positive breast cancer cells while exhibiting nearly no cytotoxicity on FRs negative normal cells. Results presented in this study were valuable to the design and fabrication of IONPs-based system for better theranostic applications.
