Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provid...Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.展开更多
There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed aga...There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.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
Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many...Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.展开更多
Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are...Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle （ADM-PBCA-NP） in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver. Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group （5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group）. A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin cOncentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector. Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups （P〈0.05）. The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of （22.3 ±6.2） nm （P〈0.05）. The ADM-PBCA-NP in （101.0±20.3） nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of （143.0±23.5） run diameter （P〈0.05）. Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBC展开更多
The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, p...The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.展开更多
Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial...Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial special bilayer structure and highly negative potential nature, therapeutic molecules have multiple difficulties in reaching mitochondria. To overcome multiple barriers for targeting mitochondria, the researchers developed various pharmaceutical preparations such as liposomes, polymeric nanoparticles and inorganic nanoparticles modified by mitochondriotropic moieties like dequalinium (DQA),triphenylphosphonium (TPP), mitochondrial penetrating peptides (MPPs) and mitochondrial protein import machinery that allow specific targeting.The targeted formulations exhibited enhanced pharmacological effect and better therapeutic effect than their untargeted counterpart both in vitro and in vivo. Nanocarriers may be used for bio-therapeutic delivery into specific mitochondria that possess a great potential treatment of mitochondria related diseases.展开更多
BACKGROUND: Targeting is a new therapeutic tool for malignant tumor as a result of combining nanotechnology with chemotherapeutics. The aim of our study was to investigate the effects of magnetic nanoparticles envelop...BACKGROUND: Targeting is a new therapeutic tool for malignant tumor as a result of combining nanotechnology with chemotherapeutics. The aim of our study was to investigate the effects of magnetic nanoparticles enveloping a chemotherapeutic drug on human cholangiocarcinoma xenografts in nude mice. METHODS: The human cholangiocarcinoma xenograft model was established in nude mice with the QBC939 cell line. The nude mice were randomly assigned to 7 groups. 0.9% saline or magnetic nanoparticles, including high (group 2), medium (group 4) and low (group 5) dosages, were given to nude mice through the tail vein 20 days after the QBC939 cell line was implanted. Calculations were made 35 days after treatment in order to compare the volumes, inhibition ratios and growth curves of the tumors in each group. Mice in each group were sacrificed randomly to collect tumor tissues and other organs for electron microscopy and pathological examination. RESULTS: The high and medium dosage groups were significantly different from the control group (P<0.05). The tumor inhibition ratios for the high, medium and low dosage groups were 39.6%, 14.6% and 7.9%, respectively. The tumor growth curve of groups 5, 4, and 2 changed slowly in turn. The high and medium groups showed cell apoptosis under an electron microscope. CONCLUSION: Magnetic nanoparticles can inhibit the growth of human cholangiocarcinoma xenografts in nude mice.展开更多
Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overe...Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.展开更多
Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-targe...Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.展开更多
In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide(Tat), producing Tat-modified Ag-F...In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide(Tat), producing Tat-modified Ag-Fe_3O_4 nanocomposites(Tat-FeAgNPs). To load drugs, an –SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin(Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed in vitro using MCF-7 cells, and in vivo using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles,with the IC_(50) of Tat-FeAgNP-Dox to be 0.63 mmol/L. The in vivo delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the in vivo optical imaging tests, in which TatFeAgNP-Cy5 yielded the most efficient accumulation in the tumor(6.772.4% ID of Tat-FeAgNPs).Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6%(P ? 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.展开更多
In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion tech...In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size,zeta potential,drug entrapment efficiency,in vitro drug release,and stability.All parameters were found to be in an acceptable range.In vitro drug release was found to be 94.1674.78%after 24 h and was fitted to the Higuchi model with a very high correlation coefficient(R2¼0.9941).Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography.The brain/blood ratio at 0.5 h for HP-SLNs i.n.,HP sol.i.n.and HP sol.i.v.was 1.61,0.17 and 0.031,respectively,indicating direct nose-to-brain transport,bypassing the blood-brain barrier.The maximum concentration(Cmax)in brain achieved from i.n.administration of HP-SLNs(329.17720.89 ng/mL,Tmax 2 h)was significantly higher than that achieved after i.v.(76.9577.62 ng/mL,Tmax 1 h),and i.n.(90.1376.28 ng/mL,Tmax 2 h)administration of HP sol.The highest drug-targeting efficiency(2362.43%)and direct transport percentage(95.77%)was found with HP-SLNs as compared to the other formulations.Higher DTE(%)and DTP(%)suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.展开更多
A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researche...A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.展开更多
superstructures has enormous potential in material sciences and engineering. Despite the potential,controlled assembly of different kinds of NPs into spatially addressable hybrid configurations still remains a formida...superstructures has enormous potential in material sciences and engineering. Despite the potential,controlled assembly of different kinds of NPs into spatially addressable hybrid configurations still remains a formidable challenge. Herein, we report a simple and universal strategy for DNA-mediated assembly of CdTe quantum dots(QDs) and lanthanide-doped upconversion nanoparticles(UCNPs). Such DNA-QD/UCNPs heterostructures not only maintains both fluorescent properties of QDs and upconversion luminescence behaviors of UCNPs, but also offers a polyvalent DNA surface, allowing for targeted dual-modality imaging of cancer cells using an aptamer. The hetero-assembly mediated by the DNA à inorganic interfacial interaction may provide a scalable way to fabricate hybrid superstructures of both theoretical and practical interests.展开更多
基金funded by the National Natural Science Foundation of China(Nos.31571016 and 81402866)
文摘Due to the ability of the blood–brain barrier(BBB) to prevent the entry of drugs into the brain, it is a challenge to treat central nervous system disorders pharmacologically. The development of nanotechnology provides potential to overcome this problem. In this review, the barriers to brain-targeted drug delivery are reviewed, including the BBB, blood–brain tumor barrier(BBTB), and nose-to-brain barrier. Delivery strategies are focused on overcoming the BBB, directly targeting diseased cells in the brain, and dual-targeted delivery. The major concerns and perspectives on constructing brain-targeted delivery systems are discussed.
基金supported by the National Natural Science Foundation of China (81472757, 81773283, 81361140344, 81600175 and 81671815)the National Basic Research Program of China (973 Program, 2013CB932502)
文摘There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels,and molecular mediators directed against harmful stimuli, is closely associated with many human diseases.As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
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.
基金financial support from the National Natural Science Foundation of China(No.81573616,81690263 and81773911,China)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20150407,China)
文摘Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood–brain barrier(BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers.Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and gliomatargeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs.The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of mentholmodified casein nanoparticles(M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-MCA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining ofthe organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.
基金This study was supported by a grant from the National 863 Program of China (No. 2002AA216011).
文摘Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle （ADM-PBCA-NP） in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver. Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group （5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group）. A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin cOncentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector. Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups （P〈0.05）. The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of （22.3 ±6.2） nm （P〈0.05）. The ADM-PBCA-NP in （101.0±20.3） nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of （143.0±23.5） run diameter （P〈0.05）. Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBC
文摘The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.
基金financially supported by the National Natural Science Foundation of China (Grant No.81473162)the Program for Liaoning Excellent Talents in Universitythe Young and middle-aged career development planning of Shenyang Pharmaceutical University
文摘Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial special bilayer structure and highly negative potential nature, therapeutic molecules have multiple difficulties in reaching mitochondria. To overcome multiple barriers for targeting mitochondria, the researchers developed various pharmaceutical preparations such as liposomes, polymeric nanoparticles and inorganic nanoparticles modified by mitochondriotropic moieties like dequalinium (DQA),triphenylphosphonium (TPP), mitochondrial penetrating peptides (MPPs) and mitochondrial protein import machinery that allow specific targeting.The targeted formulations exhibited enhanced pharmacological effect and better therapeutic effect than their untargeted counterpart both in vitro and in vivo. Nanocarriers may be used for bio-therapeutic delivery into specific mitochondria that possess a great potential treatment of mitochondria related diseases.
文摘BACKGROUND: Targeting is a new therapeutic tool for malignant tumor as a result of combining nanotechnology with chemotherapeutics. The aim of our study was to investigate the effects of magnetic nanoparticles enveloping a chemotherapeutic drug on human cholangiocarcinoma xenografts in nude mice. METHODS: The human cholangiocarcinoma xenograft model was established in nude mice with the QBC939 cell line. The nude mice were randomly assigned to 7 groups. 0.9% saline or magnetic nanoparticles, including high (group 2), medium (group 4) and low (group 5) dosages, were given to nude mice through the tail vein 20 days after the QBC939 cell line was implanted. Calculations were made 35 days after treatment in order to compare the volumes, inhibition ratios and growth curves of the tumors in each group. Mice in each group were sacrificed randomly to collect tumor tissues and other organs for electron microscopy and pathological examination. RESULTS: The high and medium dosage groups were significantly different from the control group (P<0.05). The tumor inhibition ratios for the high, medium and low dosage groups were 39.6%, 14.6% and 7.9%, respectively. The tumor growth curve of groups 5, 4, and 2 changed slowly in turn. The high and medium groups showed cell apoptosis under an electron microscope. CONCLUSION: Magnetic nanoparticles can inhibit the growth of human cholangiocarcinoma xenografts in nude mice.
基金supported by the National Basic Research Program of China(No.81573371)the Key Projects of Liaoning Province Department of Education(No.2017LZD03,China)
文摘Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.
文摘Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.
基金financial supports from National Key Research and Development Plan of China (2016YFE0119200)the Young Elite Scientists Sponsorship Program by Tianjin (No. TJSQNTJ-2017-14)National Natural Science Foundation of China (NSFC 81361140344, 21376164, 81402885, and 81373357)
文摘In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide(Tat), producing Tat-modified Ag-Fe_3O_4 nanocomposites(Tat-FeAgNPs). To load drugs, an –SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin(Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed in vitro using MCF-7 cells, and in vivo using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles,with the IC_(50) of Tat-FeAgNP-Dox to be 0.63 mmol/L. The in vivo delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the in vivo optical imaging tests, in which TatFeAgNP-Cy5 yielded the most efficient accumulation in the tumor(6.772.4% ID of Tat-FeAgNPs).Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6%(P ? 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.
文摘In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size,zeta potential,drug entrapment efficiency,in vitro drug release,and stability.All parameters were found to be in an acceptable range.In vitro drug release was found to be 94.1674.78%after 24 h and was fitted to the Higuchi model with a very high correlation coefficient(R2¼0.9941).Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography.The brain/blood ratio at 0.5 h for HP-SLNs i.n.,HP sol.i.n.and HP sol.i.v.was 1.61,0.17 and 0.031,respectively,indicating direct nose-to-brain transport,bypassing the blood-brain barrier.The maximum concentration(Cmax)in brain achieved from i.n.administration of HP-SLNs(329.17720.89 ng/mL,Tmax 2 h)was significantly higher than that achieved after i.v.(76.9577.62 ng/mL,Tmax 1 h),and i.n.(90.1376.28 ng/mL,Tmax 2 h)administration of HP sol.The highest drug-targeting efficiency(2362.43%)and direct transport percentage(95.77%)was found with HP-SLNs as compared to the other formulations.Higher DTE(%)and DTP(%)suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.
基金supported by the Natural Science Foundation of Beijing,No.L222126(to LD)。
文摘A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.
基金supported financially by the National Natural Science Foundation of China (Nos. 21822401, 21771044)the Young Thousand Talented Program
文摘superstructures has enormous potential in material sciences and engineering. Despite the potential,controlled assembly of different kinds of NPs into spatially addressable hybrid configurations still remains a formidable challenge. Herein, we report a simple and universal strategy for DNA-mediated assembly of CdTe quantum dots(QDs) and lanthanide-doped upconversion nanoparticles(UCNPs). Such DNA-QD/UCNPs heterostructures not only maintains both fluorescent properties of QDs and upconversion luminescence behaviors of UCNPs, but also offers a polyvalent DNA surface, allowing for targeted dual-modality imaging of cancer cells using an aptamer. The hetero-assembly mediated by the DNA à inorganic interfacial interaction may provide a scalable way to fabricate hybrid superstructures of both theoretical and practical interests.
