Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and ...Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.展开更多
Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional dif...Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.展开更多
Bloode-brain barrier(BBB)strictly controls matter exchange between blood and brain,and severely limits brain penetration of systemically administered drugs,resulting in ineffective drug therapy of brain diseases.Howev...Bloode-brain barrier(BBB)strictly controls matter exchange between blood and brain,and severely limits brain penetration of systemically administered drugs,resulting in ineffective drug therapy of brain diseases.However,during the onset and progression of brain diseases,BBB alterations evolve inevitably.In this review,we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer’s disease,Parkinson’s disease,epilepsy,stroke,traumatic brain injury and brain tumor.The advances on optimization of small molecules for BBB crossing and non-systemic administration routes(e.g.,intranasal treatment)for BBB bypassing are not included in this review.展开更多
Ultrasonic imaging is becoming the most popular medical imaging modality,owing to the low price per examination and its safety.However,blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit freq...Ultrasonic imaging is becoming the most popular medical imaging modality,owing to the low price per examination and its safety.However,blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies.For perfusion imaging,markers have been designed to enhance the contrast in B-mode imaging.These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells.In this review,the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described.Furthermore,an outline of clinical imaging applications of contrast-enhanced ultrasound is given.It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition,and how these phenomena may be utilized in ultrasonic imaging.Aided by high-speed photography,our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques.More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves,and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs.These are beginning to be accepted into clinical practice.In the long term,targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested.展开更多
OBJECTIVE: To explore the role of Traditional Chinese Medicine(TCM) in the prevention and treatment of colorectal cancer and identify possible therapeutic targets of TCM to provide clues for the use of TCM for colorec...OBJECTIVE: To explore the role of Traditional Chinese Medicine(TCM) in the prevention and treatment of colorectal cancer and identify possible therapeutic targets of TCM to provide clues for the use of TCM for colorectal cancer prevention and treatment in the clinic and to find novel directions for new drug discovery for colorectal cancer.METHODS: We used Pub Med and Google to search for and collect scientific publications for a full evaluation of current evidence in the literature indicating the potential role of Chinese herbal medicines and their respective ingredients as effective candidatesforcolorectalcancerpreventionandtreatment.RESULTS: We extracted a detailed description of potential therapeutic Chinese herbal medicines and their constituent ingredients that target different mechanisms in colorectal cancer such as gene mutation, dysregulation of signaling pathways, metabolism disorders, and the inflammatory microenvironment, including both conventional and non-conventional approaches.CONCLUSION: TCM may be a promising complementary and alternative therapy for the treatment of colorectal cancer.展开更多
AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutam...AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutamate(PLG).METHODS:The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl 4.The expression level of Kal was measured.The serum biomarker levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malonyldialdehyde(MDA),and tumor necrosis factor(TNF)-α were monitored.The extent of CCl 4-induced liver injury was analyzed histopathologically.RESULTS:The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation.In the Kal gene-transferred mice,protection against CCl 4-induced liver injury was reflected by significantly decreased serum ALT,AST,MDA and TNF-α levels compared to those in control mice(P < 0.01 to 0.05 in a dose-dependent manner).Histological observations also revealed that hepatocyte necrosis,hemorrhage,vacuolar change and hydropic degeneration were apparent in mice after CCl 4 administration.In contrast,the damage was markedly attenuated in the Kal gene-transferred mice.The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice.CONCLUSION:Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl 4-induced oxidative stress and inflammatory response,and reduced the liver damage in a mouse model.展开更多
Nanotechnologies have been successfully applied to the treatment of various diseases.Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in d...Nanotechnologies have been successfully applied to the treatment of various diseases.Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects.In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.展开更多
Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been som...Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.展开更多
文摘Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.
基金supported by the Drug Innovation Major Project(2018ZX09711001-002-005,China)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2017-I2M-1-011,China)+1 种基金National Natural Science Foundation of China(No.82073778,China)Fundamental Research Funds for the Central Public Welfare Research Institutes(2018PT35002,China)
文摘Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.
基金funded by the international cooperative project of the National Key R&D Program of China(No.2017YFE0126900)the National Natural Science Foundation of China(No.81703428 and No.81973254)+2 种基金the Natural Science Foundation of Jiangsu Province(No.BK20191421,China)the Suzhou Science and Technology Development Project(No.SYS2019033,China)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD,China)
文摘Bloode-brain barrier(BBB)strictly controls matter exchange between blood and brain,and severely limits brain penetration of systemically administered drugs,resulting in ineffective drug therapy of brain diseases.However,during the onset and progression of brain diseases,BBB alterations evolve inevitably.In this review,we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer’s disease,Parkinson’s disease,epilepsy,stroke,traumatic brain injury and brain tumor.The advances on optimization of small molecules for BBB crossing and non-systemic administration routes(e.g.,intranasal treatment)for BBB bypassing are not included in this review.
文摘Ultrasonic imaging is becoming the most popular medical imaging modality,owing to the low price per examination and its safety.However,blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies.For perfusion imaging,markers have been designed to enhance the contrast in B-mode imaging.These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells.In this review,the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described.Furthermore,an outline of clinical imaging applications of contrast-enhanced ultrasound is given.It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition,and how these phenomena may be utilized in ultrasonic imaging.Aided by high-speed photography,our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques.More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves,and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs.These are beginning to be accepted into clinical practice.In the long term,targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested.
基金Supported by National Natural Science Foundation of China(Research for the Mechanism of Fei-Liu-Ping Ointment Regulating Tumor Inflammatory Microenvironment to Prevent Lung Cancer Metastasis,No.81273718)China Postdoctoral Science Foundation(In vitro study on Fei-Liu-Ping ointment preventing lung cancer metastasis caused by inflammatory microenvironment,No.2012T50199)
文摘OBJECTIVE: To explore the role of Traditional Chinese Medicine(TCM) in the prevention and treatment of colorectal cancer and identify possible therapeutic targets of TCM to provide clues for the use of TCM for colorectal cancer prevention and treatment in the clinic and to find novel directions for new drug discovery for colorectal cancer.METHODS: We used Pub Med and Google to search for and collect scientific publications for a full evaluation of current evidence in the literature indicating the potential role of Chinese herbal medicines and their respective ingredients as effective candidatesforcolorectalcancerpreventionandtreatment.RESULTS: We extracted a detailed description of potential therapeutic Chinese herbal medicines and their constituent ingredients that target different mechanisms in colorectal cancer such as gene mutation, dysregulation of signaling pathways, metabolism disorders, and the inflammatory microenvironment, including both conventional and non-conventional approaches.CONCLUSION: TCM may be a promising complementary and alternative therapy for the treatment of colorectal cancer.
基金Supported by The State High Technology Research and Development Program of China (863 Program),No.2008AA02Z135the Important National Science and Technology Specific Projects,No.2009ZX09103-643the Natural Science Foundation of China,No.30973591
文摘AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutamate(PLG).METHODS:The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl 4.The expression level of Kal was measured.The serum biomarker levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malonyldialdehyde(MDA),and tumor necrosis factor(TNF)-α were monitored.The extent of CCl 4-induced liver injury was analyzed histopathologically.RESULTS:The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation.In the Kal gene-transferred mice,protection against CCl 4-induced liver injury was reflected by significantly decreased serum ALT,AST,MDA and TNF-α levels compared to those in control mice(P < 0.01 to 0.05 in a dose-dependent manner).Histological observations also revealed that hepatocyte necrosis,hemorrhage,vacuolar change and hydropic degeneration were apparent in mice after CCl 4 administration.In contrast,the damage was markedly attenuated in the Kal gene-transferred mice.The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice.CONCLUSION:Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl 4-induced oxidative stress and inflammatory response,and reduced the liver damage in a mouse model.
基金supported by the National Natural Science Foundation of China (No. 81773911, 81690263 and 81573616)the Development Project of Shanghai Peak DisciplinesIntegrated Medicine (No. 20180101)。
文摘Nanotechnologies have been successfully applied to the treatment of various diseases.Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects.In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.
文摘Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.
