CONSPECTUS:Nature presents us with numerous complex topological structures,among which ordered bicontinuous structures are widely found in biological systems and exhibit numerous functions,as exemplified by the vibran...CONSPECTUS:Nature presents us with numerous complex topological structures,among which ordered bicontinuous structures are widely found in biological systems and exhibit numerous functions,as exemplified by the vibrant wings of butterflies and the robust skeletons of knobby starfish.In recent decades,significant strides have been made in preparing functional materials with bicontinuous porous structures,e.g.,cubosomes�spherical colloidal particles,which encompass continuous pores and frameworks arranged in a cubic crystal lattice.These cubosomes exhibit many remarkable advantages due to their unique periodic topological structure.(1)The three-dimensional(3D)interconnected pores facilitate the smooth transport of substances throughout the material,resulting in at least a three times higher utilization ratio of internal active sites compared to that of their unconnected pore or nonporous counterparts.Their complex,tortuous,and periodic porous configuration can enhance energy capture,such as solar/electric energy.(2)The 3D continuous pore channels and frameworks provide“highways”for ion and electron transport,leading to an order-of-magnitude reduction in charge-transfer resistance and an over 3-fold increase in the ion diffusion coefficient compared to those of nonporous analogues,thereby improving the electrochemical kinetics of electrodes.(3)Cubosomes have emerged as unique mechanical metamaterials,exhibiting a remarkable capability to alleviate mechanical stress and strain.(4)Their negative-Gaussian-curvature surfaces facilitate the adsorption/desorption of reaction intermediates,thereby lowering the reaction free energy in catalytic reaction processes.Additionally,this distinctive surface structure can enhance the electric field intensity at material interfaces,significantly promoting ion adsorption.With these advantages,functional cubosomes show potential for application in the field of energy storage and conversion.However,due to the big challenges in their preparation,there have been limited studies on their structure−activity relationships in energy-related applications.Therefore,there has not yet been a review regarding functional cubosomes.In this Account,we summarize mainly our latest progress in the study of functional cubosomes.First,we introduce the preparation of polymer cubosomes(PCs)through the self-assembly of block copolymers in solution,along with plotting their morphological phase diagram.Then,the Account describes nanocasting approaches in which polymer cubosomes are employed as templates to prepare a variety of functional cubosomes,including polymers,covalent organic frameworks(COFs),metal−organic frameworks(MOFs),metal−phenolic networks,carbons,inorganic metal compounds,and metals.Finally,to elucidate the application prospects of the functional cubosomes,this Account discusses their advantages in different energy storage and conversion applications,highlighting efficient material and energy utilization,fast mass and electron transport,negative-Gaussian-curvature surfaces,and excellent mechanical stability.We anticipate that this Account will demystify functional cubosomes with bicontinuous porous structures and stimulate their broad interest in the fields of materials science,chemistry,and energy,among others.展开更多
The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil(5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase...The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil(5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer.Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly(Po 0.05) increased5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution.However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.展开更多
The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally s...The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.展开更多
Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug deliver...Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug delivery nanocarriers by virtue of their biocompatibility and bioadhesion,sizeable payload encapsulation and high thermostability.Herein,an active tumour targeting system towards rhabdomyosarcoma(RMS)cells was evaluated.Cubosomes were loaded with helenalin(a secondary metabolite from Arnica plants),which we have previously shown to induce apoptosis in RMS cells.The functionalization of the cubosomes was accomplished to enable binding to membrane receptors and translocation under a magnetic field.RMS cells overexpress CD44 and CD221 on their membrane surface and,therefore,hyaluronic acid(HA,a ligand for CD44)and antibodies(Abs)against CD221 were coupled to cubosomes via electrostatic attraction and the thiol-Michael reaction,respectively.Magnetization of the cubic phase NPs was achieved by embedding superparamagnetic iron oxide NPs(SPIONPs)into the cubic matrix.Single-function and multi-function cubosomes had Im3m cubic phase structures with well-organized lattice patterns.Conjugation with 2%HA or anti-CD221 half Abs and/or 1%SPIONPs showed significantly higher uptake into RMS cells compared to unfunctionalized cubosomes.CD44 and CD221 directed magnetic(triple-function)cubosomes were capable of internalizing into RMS cells in an energy-independent mechanism.Helenalin-laden triple functionalized cubosomes showed limited impact on the viability of control fibroblast cells,while they induced a high degree cytotoxicity against RMS cells.Profound tumour cell death was observed in both two-dimensional(2D)culture and three-dimensional(3D)tumour spheroids.展开更多
It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which ...It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which is the function of their ability to cross the membrane, tends to be low and exhibit high intra and inter subject variability. At present, formulation scientists are pursuing many projects for transdermal, nasal, target delivery of many active compounds, and it is prudent to explore alternative possibilities. Cubosomes offer transportation and tailoring of active compounds intended for both systemic and dermal delivery. Cubosomes are dispersed, self-assembled nanoparticles of bicontinuous cubic liquid crystalline phase formed from lipid and surfactant systems. Monoolein, poloxamer 407 and polyvinyl alcohol are the mostly used ingredients in the formulation of cubosomes. The adjustment in lipid composition can control the internal and structural changes of cubosomes. Based on the nodal surfaces, three structures of cubosomes proposed are Pn3m, Ia3d and Im3m. Top-down and bottom-up techniques are widely considered in the formulation process of extreme viscous bulk phase and aggregate from a precursor respectively. This article gives a bird's eye view about the engineering, characterization and evaluation of cubosomes, covering researches and applications of cubosomes done till date.展开更多
Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species.Here,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized wit...Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species.Here,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127.Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis.To monitor the therapeutic effect of the ELC nanocarrier,we apply for the first time,label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier.Improved in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu).Importantly,for equivalent copper concentration,cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug.The novel nanocarrier shows promising features for systemic ELC-Cu administration,and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.展开更多
Polymerization-induced cooperative assembly(PICA)is reported to efficiently access inverse bicontinuous mesophases within particles consisting of amphiphilic block copolymers(BCPs)and solvophobic copolymers.Reversible...Polymerization-induced cooperative assembly(PICA)is reported to efficiently access inverse bicontinuous mesophases within particles consisting of amphiphilic block copolymers(BCPs)and solvophobic copolymers.Reversible addition-fragmentation chain transfer(RAFT)dispersion alternating copolymerization of styrene and pentafluorostyrene is conducted in 2%v/v toluene/ethanol by simultaneously using poly(N,N-dimethylacrylamide)(PDMA29)as a macromolecular chain transfer agent(macro-CTA)and small molecule CTA.展开更多
基金supported by the National Natural Science Foundation of China(22225501,W2412102,52421006,22305149,52303275,and 52203268)the Shanghai Municipal Science and Technology Major Project,and SJTU 2030B plan(WH510207202).
文摘CONSPECTUS:Nature presents us with numerous complex topological structures,among which ordered bicontinuous structures are widely found in biological systems and exhibit numerous functions,as exemplified by the vibrant wings of butterflies and the robust skeletons of knobby starfish.In recent decades,significant strides have been made in preparing functional materials with bicontinuous porous structures,e.g.,cubosomes�spherical colloidal particles,which encompass continuous pores and frameworks arranged in a cubic crystal lattice.These cubosomes exhibit many remarkable advantages due to their unique periodic topological structure.(1)The three-dimensional(3D)interconnected pores facilitate the smooth transport of substances throughout the material,resulting in at least a three times higher utilization ratio of internal active sites compared to that of their unconnected pore or nonporous counterparts.Their complex,tortuous,and periodic porous configuration can enhance energy capture,such as solar/electric energy.(2)The 3D continuous pore channels and frameworks provide“highways”for ion and electron transport,leading to an order-of-magnitude reduction in charge-transfer resistance and an over 3-fold increase in the ion diffusion coefficient compared to those of nonporous analogues,thereby improving the electrochemical kinetics of electrodes.(3)Cubosomes have emerged as unique mechanical metamaterials,exhibiting a remarkable capability to alleviate mechanical stress and strain.(4)Their negative-Gaussian-curvature surfaces facilitate the adsorption/desorption of reaction intermediates,thereby lowering the reaction free energy in catalytic reaction processes.Additionally,this distinctive surface structure can enhance the electric field intensity at material interfaces,significantly promoting ion adsorption.With these advantages,functional cubosomes show potential for application in the field of energy storage and conversion.However,due to the big challenges in their preparation,there have been limited studies on their structure−activity relationships in energy-related applications.Therefore,there has not yet been a review regarding functional cubosomes.In this Account,we summarize mainly our latest progress in the study of functional cubosomes.First,we introduce the preparation of polymer cubosomes(PCs)through the self-assembly of block copolymers in solution,along with plotting their morphological phase diagram.Then,the Account describes nanocasting approaches in which polymer cubosomes are employed as templates to prepare a variety of functional cubosomes,including polymers,covalent organic frameworks(COFs),metal−organic frameworks(MOFs),metal−phenolic networks,carbons,inorganic metal compounds,and metals.Finally,to elucidate the application prospects of the functional cubosomes,this Account discusses their advantages in different energy storage and conversion applications,highlighting efficient material and energy utilization,fast mass and electron transport,negative-Gaussian-curvature surfaces,and excellent mechanical stability.We anticipate that this Account will demystify functional cubosomes with bicontinuous porous structures and stimulate their broad interest in the fields of materials science,chemistry,and energy,among others.
文摘The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil(5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer.Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly(Po 0.05) increased5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution.However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.
基金Financial support to Anan Yaghmur for studies on development of drug nanocarriers based on cubosomes and hexosomes by the Danish Council for Independent Research|Technology and Production Sciences(references 1335-00150b and DFF-7017-00065,Denmark)。
文摘The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.
基金supported by the Pyongyang University of Science and Technology(PUST)-UK scholarship,the Williams Fund(Oxford Hospitals Charity,No.0085)the UK national electron bio-imaging centre(No.NT32452)the Marie Sklodowska–Curie Grant Agreement(No.840964).
文摘Confining chemotherapy to tumour sites by means of active targeting nanoparticles(NPs)may increase the treatment effectuality while reducing potential side effects.Cubosomes are one of the next-generation drug delivery nanocarriers by virtue of their biocompatibility and bioadhesion,sizeable payload encapsulation and high thermostability.Herein,an active tumour targeting system towards rhabdomyosarcoma(RMS)cells was evaluated.Cubosomes were loaded with helenalin(a secondary metabolite from Arnica plants),which we have previously shown to induce apoptosis in RMS cells.The functionalization of the cubosomes was accomplished to enable binding to membrane receptors and translocation under a magnetic field.RMS cells overexpress CD44 and CD221 on their membrane surface and,therefore,hyaluronic acid(HA,a ligand for CD44)and antibodies(Abs)against CD221 were coupled to cubosomes via electrostatic attraction and the thiol-Michael reaction,respectively.Magnetization of the cubic phase NPs was achieved by embedding superparamagnetic iron oxide NPs(SPIONPs)into the cubic matrix.Single-function and multi-function cubosomes had Im3m cubic phase structures with well-organized lattice patterns.Conjugation with 2%HA or anti-CD221 half Abs and/or 1%SPIONPs showed significantly higher uptake into RMS cells compared to unfunctionalized cubosomes.CD44 and CD221 directed magnetic(triple-function)cubosomes were capable of internalizing into RMS cells in an energy-independent mechanism.Helenalin-laden triple functionalized cubosomes showed limited impact on the viability of control fibroblast cells,while they induced a high degree cytotoxicity against RMS cells.Profound tumour cell death was observed in both two-dimensional(2D)culture and three-dimensional(3D)tumour spheroids.
文摘It is challenging for many drugs to be transported across various biological membranes. Furthermore, development of many drugs gets thwarted owing to their hydrophilic nature. The bioavailability of such drugs, which is the function of their ability to cross the membrane, tends to be low and exhibit high intra and inter subject variability. At present, formulation scientists are pursuing many projects for transdermal, nasal, target delivery of many active compounds, and it is prudent to explore alternative possibilities. Cubosomes offer transportation and tailoring of active compounds intended for both systemic and dermal delivery. Cubosomes are dispersed, self-assembled nanoparticles of bicontinuous cubic liquid crystalline phase formed from lipid and surfactant systems. Monoolein, poloxamer 407 and polyvinyl alcohol are the mostly used ingredients in the formulation of cubosomes. The adjustment in lipid composition can control the internal and structural changes of cubosomes. Based on the nodal surfaces, three structures of cubosomes proposed are Pn3m, Ia3d and Im3m. Top-down and bottom-up techniques are widely considered in the formulation process of extreme viscous bulk phase and aggregate from a precursor respectively. This article gives a bird's eye view about the engineering, characterization and evaluation of cubosomes, covering researches and applications of cubosomes done till date.
文摘Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species.Here,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127.Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis.To monitor the therapeutic effect of the ELC nanocarrier,we apply for the first time,label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier.Improved in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu).Importantly,for equivalent copper concentration,cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug.The novel nanocarrier shows promising features for systemic ELC-Cu administration,and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.
基金support by the National Natural Science Foundation of China(nos.51733003 and 21674059)the Fundamental Research Funds for the Central Universities are thanked.
文摘Polymerization-induced cooperative assembly(PICA)is reported to efficiently access inverse bicontinuous mesophases within particles consisting of amphiphilic block copolymers(BCPs)and solvophobic copolymers.Reversible addition-fragmentation chain transfer(RAFT)dispersion alternating copolymerization of styrene and pentafluorostyrene is conducted in 2%v/v toluene/ethanol by simultaneously using poly(N,N-dimethylacrylamide)(PDMA29)as a macromolecular chain transfer agent(macro-CTA)and small molecule CTA.
