Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical applicatio...Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.展开更多
Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxybutyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polym...Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxybutyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polymerization. The structures are confirmed by gel permeation chromatography and NMR analyses. Crystallization investigated by X-ray diffraction reveals that the block copolymer with higher content of poly(ethyl ethylene phosphate) (PEEP) is more amorphous, showing decreased crystallizability. The obtained copolymers self-assemble into biodegradable nanoparticles with a coreshell micellar structure in aqueous solution, verified by the probe-based fluorescence measurements and transmission electronic microscopy (TEM) observation. The hydrophobic poly(3-hydroxybutyrate) (PHB) block serves as the core of the micelles and the micelles are stabilized by the hydrophilic PEEP block. The size and size distribution are related to the compositions of the copolymers. Paclitaxel (PTX) has been encapsulated into the micelles as a model drug and a sustained drug release from the micelles is observed. MTT assay also demonstrates that the block copolymers are biocompatible, rendering these copolymers attractive for drug delivery.展开更多
The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past decades.Here we unexpectedly observed the similar"EPR effect"at the site of iniury.W...The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past decades.Here we unexpectedly observed the similar"EPR effect"at the site of iniury.We found that the temporary dilated and leaky blood vessels caused by the potent vasodilator histamine in response to injury allowed the injected nanoparticles to pass through the vasculature and reached the injured tissue.Our finding shows the potential underline mechanism of"EPR effect"at the injured site.By loading with antibiotics,we further demonstrated a new strategy for prevention of infection at the site of injury.展开更多
Pigment nanoparticles with a size range of 10~100 nm were produced from large agglomerates via a stirred media mill operating in the wet-batch mode and using polymeric media. The effects of several operating variables...Pigment nanoparticles with a size range of 10~100 nm were produced from large agglomerates via a stirred media mill operating in the wet-batch mode and using polymeric media. The effects of several operating variables such as the surfactant concentration, polystyrene media loading, and media size on the pigment size distribution of the product were studied. The process dynamics was also investigated. Dynamic light scattering and electron microscopy were used as the characterization techniques. The polymeric grinding media are found to be effective for the production of pigment nanoparticles. The experimental results suggest the existence of an optimum media size and surfactant concentration. A population balance model of the process reveals a transition from first-order breakage kinetics for rela-tively coarse particles to non-first-order kinetics, with a delay period, for the smaller particles. The model implies that large agglomerates split in a first-order fashion whereas the breakage of individual nanoparticles may depend on induced fatigue of the particles.展开更多
Objective:To prepare curcumin-piperine(Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation o...Objective:To prepare curcumin-piperine(Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.Methods:Cu-Pi nanoparticles were prepared by thin film hydration method,solid dispersion method,emulsion polymerization method and Fessi method.Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles.Results:Out of four methods,Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV.Change of organic solvent(acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles.However,increase in sonication time,stirring speed,viscosity,use of 1:10:10 ratio of drag/polymer/surfactant,and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles.Conclusions:Cu-Pi nanoparticles coated with PEC containing copolymer produced by Fessi method had a minimum average particle size,excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study.This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.展开更多
Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism ...Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.展开更多
ABSTRACT Rationally designing broad-spectrum photocatalysts to harvest whole visible-light region photons and enhance solar energy conversion is a“holy grail”for researchers,but is still a challenging issue.Herein,b...ABSTRACT Rationally designing broad-spectrum photocatalysts to harvest whole visible-light region photons and enhance solar energy conversion is a“holy grail”for researchers,but is still a challenging issue.Herein,based on the common polymeric carbon nitride(PCN),a hybrid co-catalysts system comprising plasmonic Au nanoparticles(NPs)and atomically dispersed Pt single atoms(PtSAs)with different functions was constructed to address this challenge.For the dual co-catalysts decorated PCN(PtSAs–Au_(2.5)/PCN),the PCN is photoexcited to generate electrons under UV and short-wavelength visible light,and the synergetic Au NPs and PtSAs not only accelerate charge separation and transfer though Schottky junctions and metal-support bond but also act as the co-catalysts for H_(2) evolution.Furthermore,the Au NPs absorb long-wavelength visible light owing to its localized surface plasmon resonance,and the adjacent PtSAs trap the plasmonic hot-electrons for H_(2) evolution via direct electron transfer effect.Consequently,the PtSAs–Au_(2.5)/PCN exhibits excellent broad-spectrum photocatalytic H_(2) evolution activity with the H_(2) evolution rate of 8.8 mmol g^(−1) h^(−1) at 420 nm and 264μmol g^(−1) h^(−1) at 550 nm,much higher than that of Au_(2.5)/PCN and PtSAs–PCN,respectively.This work provides a new strategy to design broad-spectrum photocatalysts for energy conversion reaction.展开更多
The aggregation-caused quenching(ACQ)rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences.However,its usefulness is undermined by limi...The aggregation-caused quenching(ACQ)rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences.However,its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-Ⅰ(700-900 nm)bioimaging owing to absorption and diffraction by biological tissues and tissue-derived autofluorescence.This study aimed to develop ACQ-based NIR-Ⅱ(1000-1700 nm)probes to further improve the imaging resolution and accuracy.The strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent effects.The newly developed probes displayed remarkable photophysical properties,with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm region.Compared with the NIR-Ⅰ counterpart P2,the NIR-Ⅱ probes demonstrated superior water sensitivity and quenching stability.ACQ1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of incubation.Theoretical calculations verified that molecular planarity is more important than hydrophobicity for ACQ properties.Additionally,in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1,in contrast to 15% for P2.展开更多
Hyaluronic acid(HA, 20–50 kDa) is a hydrophilic macromolecule with anti-wrinkle effects and moisturizing properties. However, its high molecular weight prevents it from penetrating into the deeper layers of the skin ...Hyaluronic acid(HA, 20–50 kDa) is a hydrophilic macromolecule with anti-wrinkle effects and moisturizing properties. However, its high molecular weight prevents it from penetrating into the deeper layers of the skin and, thus, limits its benefits to topical effects. Thus, the objective of this study is to prepare nanoparticles of quaternized cyclodextrin-grafted chitosan(QCD-g-CS) associated with HA in different molar ratios of QCD-g-CS and HA. The conjugation of the carboxylic moieties of HA and the amides of QCD-g-CS was confirmed by Fourier-transform infrared spectroscopy. Thus, the system was optimized to create nanoparticles with a small size(235.63 ± 21.89 nm), narrow polydispersity index(0.13 ± 0.02), and zeta potential of 16.07 ± 0.65 m V. The association efficiency and loading efficiency were determined by ultra-performance liquid chromatography as 86.77 ± 0.69% and 10.85 ± 0.09%, respectively. The spherical morphology of the obtained nanoparticles was confirmed by transmission electron microscopy. Moreover, the in-vitro hydrating ability was significantly higher( P < 0.001) than that of bulk HA(3.29 ± 0.41 and 1.71 ± 0.05 g water/g sample, respectively). The safety of these nanoparticles at concentrations in the range of 0.01–0.10 mg/ml was confirmed via tests on human skin fibroblasts. Together, these results demonstrate that the developed nanoparticles are promising for future applications in cosmetics.展开更多
Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic ...Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for cancers.However,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake.Therefore,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA delivery.In this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer immunotherapies.We also highlight promising treatment regimens and their clinical translation.展开更多
Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-fo...Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-folding cyclization technique at high concentrations.Linear poly((oligo(ethylene glycol)acrylate)-co-(dodecyl acrylate))(P(OEGA-co-DDA))precursors with different ratios of hydrophilic and hydrophobic moieties were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization using a bifunctional chain transfer agent with two anthryl end groups.The amphiphilic linear precursors underwent the self-folding process to generate polymeric nanoparticles in water.By irradiating the aqueous solution of the nanoparticles with 365 nm UV light,cyclic polymers were synthesized successfully via coupling of anthryl groups.The effects of the ratios of hydrophilic and hydrophobic moieties in linear P(OEGA-co-DDA)copolymers and polymer concentration on the purity of the obtained cyclic polymers were explored in detail via ^(1)H nuclear magnetic resonance(^(1)H NMR),dynamic light scattering(DLS),UV‒visible(vis)analysis,three-detection size exclusion chromatography(TD-SEC)and transmission electron microscopy(TEM).It was found that by adjusting the content of the hydrophilic segments in linear precursors,single chain polymeric nanoparticles(SCPNs)can be generated at high polymer concentrations.Therefore,cyclic polymers with high purity can be constructed efficiently.This method overcomes the limitation of traditional ring-closure method,which is typically conducted in highly dilute conditions,providing an efficient method for the scalable preparation of cyclic polymers.展开更多
Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generati...Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ~80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (~0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H_(2)O_(2) into O_(2) to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.展开更多
Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered dru...Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered drug delivery,and real-time monitoring of therapeutic response.Particularly,tumor microenvironment(TME)-responsive polymeric nanocarriers in response to weak acidity,hypoxia,reactive oxygen species(ROS),glutathione(GSH),or tumor enzymes in the TME show great promise in facilitating tumor accumulation,enhancing tumor penetration,prolonging tumor retention,and achieving controlled drug release,thereby improving the efficiency of tumor therapy.Besides,the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors,which allows for the integration of the advantages of each treatment modality,addressing the shortcomings of the two methods,and amplifying the efficacy of tumor treatment while reducing adverse reactions.This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy,and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.展开更多
基金Acknowledgments This work was supported by the National Basic Research Program of China （2012CB934004）, the National Funds for Distinguished Young Scientists （31325010）, the Key Research Program of the Chinese Academy of Sciences （KGZD-EW-T06） and the National Natural Science Foundation of China （31300822）.
文摘Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.
基金Supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No.20060358036)
文摘Biodegradable and amphiphilic triblock copolymers poly(ethyl ethylene phosphate)-poly(3-hydroxybutyrate)-poly(ethyl ethylene phosphate) (PEEP-b-PHB-b-PEEP) have been successfully synthesized through ring-opening polymerization. The structures are confirmed by gel permeation chromatography and NMR analyses. Crystallization investigated by X-ray diffraction reveals that the block copolymer with higher content of poly(ethyl ethylene phosphate) (PEEP) is more amorphous, showing decreased crystallizability. The obtained copolymers self-assemble into biodegradable nanoparticles with a coreshell micellar structure in aqueous solution, verified by the probe-based fluorescence measurements and transmission electronic microscopy (TEM) observation. The hydrophobic poly(3-hydroxybutyrate) (PHB) block serves as the core of the micelles and the micelles are stabilized by the hydrophilic PEEP block. The size and size distribution are related to the compositions of the copolymers. Paclitaxel (PTX) has been encapsulated into the micelles as a model drug and a sustained drug release from the micelles is observed. MTT assay also demonstrates that the block copolymers are biocompatible, rendering these copolymers attractive for drug delivery.
基金This work was supported by grants from startup supports of Soochow University and the Program for Jiangsu Specially-Appointed Professors.This work was also supported by the National Natural Science Foundation of China(No.31900988)the Natural Science Foundation of Jiangsu Province(No.SBK2019040088).
文摘The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past decades.Here we unexpectedly observed the similar"EPR effect"at the site of iniury.We found that the temporary dilated and leaky blood vessels caused by the potent vasodilator histamine in response to injury allowed the injected nanoparticles to pass through the vasculature and reached the injured tissue.Our finding shows the potential underline mechanism of"EPR effect"at the injured site.By loading with antibiotics,we further demonstrated a new strategy for prevention of infection at the site of injury.
文摘Pigment nanoparticles with a size range of 10~100 nm were produced from large agglomerates via a stirred media mill operating in the wet-batch mode and using polymeric media. The effects of several operating variables such as the surfactant concentration, polystyrene media loading, and media size on the pigment size distribution of the product were studied. The process dynamics was also investigated. Dynamic light scattering and electron microscopy were used as the characterization techniques. The polymeric grinding media are found to be effective for the production of pigment nanoparticles. The experimental results suggest the existence of an optimum media size and surfactant concentration. A population balance model of the process reveals a transition from first-order breakage kinetics for rela-tively coarse particles to non-first-order kinetics, with a delay period, for the smaller particles. The model implies that large agglomerates split in a first-order fashion whereas the breakage of individual nanoparticles may depend on induced fatigue of the particles.
基金financially supported by UGC Sanction order No.F.4-1/2006(BSR)/7-269/2009(BSR)
文摘Objective:To prepare curcumin-piperine(Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.Methods:Cu-Pi nanoparticles were prepared by thin film hydration method,solid dispersion method,emulsion polymerization method and Fessi method.Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles.Results:Out of four methods,Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV.Change of organic solvent(acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles.However,increase in sonication time,stirring speed,viscosity,use of 1:10:10 ratio of drag/polymer/surfactant,and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles.Conclusions:Cu-Pi nanoparticles coated with PEC containing copolymer produced by Fessi method had a minimum average particle size,excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study.This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.
基金the NEVET Nanotechnology Grant of the Russell Berrie Nanotechnology Institute(RBNI)at Technion—Israel Institute of Technology(Israel)the Tamara and Harry Handelsman Academic Chair(Israel)for financial support。
文摘Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.
基金supported by the National Natural Science Foundation of China(Grant No.51871078 and 52071119)Interdisciplinary Research Foundation of HIT(Grant No.IR2021208)+1 种基金State Key Laboratory of Urban Water Resource and Environment(Harbin Institute of Technology)(No.2022TS38)Heilongjiang Science Foundation(No.LH2020B006).
文摘ABSTRACT Rationally designing broad-spectrum photocatalysts to harvest whole visible-light region photons and enhance solar energy conversion is a“holy grail”for researchers,but is still a challenging issue.Herein,based on the common polymeric carbon nitride(PCN),a hybrid co-catalysts system comprising plasmonic Au nanoparticles(NPs)and atomically dispersed Pt single atoms(PtSAs)with different functions was constructed to address this challenge.For the dual co-catalysts decorated PCN(PtSAs–Au_(2.5)/PCN),the PCN is photoexcited to generate electrons under UV and short-wavelength visible light,and the synergetic Au NPs and PtSAs not only accelerate charge separation and transfer though Schottky junctions and metal-support bond but also act as the co-catalysts for H_(2) evolution.Furthermore,the Au NPs absorb long-wavelength visible light owing to its localized surface plasmon resonance,and the adjacent PtSAs trap the plasmonic hot-electrons for H_(2) evolution via direct electron transfer effect.Consequently,the PtSAs–Au_(2.5)/PCN exhibits excellent broad-spectrum photocatalytic H_(2) evolution activity with the H_(2) evolution rate of 8.8 mmol g^(−1) h^(−1) at 420 nm and 264μmol g^(−1) h^(−1) at 550 nm,much higher than that of Au_(2.5)/PCN and PtSAs–PCN,respectively.This work provides a new strategy to design broad-spectrum photocatalysts for energy conversion reaction.
基金supported by the National Natural Science Foundation of China(Nos.82273867 and 82030107)the Science and Technology Commission of Shanghai Municipality(No.21430760800,China).
文摘The aggregation-caused quenching(ACQ)rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences.However,its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-Ⅰ(700-900 nm)bioimaging owing to absorption and diffraction by biological tissues and tissue-derived autofluorescence.This study aimed to develop ACQ-based NIR-Ⅱ(1000-1700 nm)probes to further improve the imaging resolution and accuracy.The strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent effects.The newly developed probes displayed remarkable photophysical properties,with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm region.Compared with the NIR-Ⅰ counterpart P2,the NIR-Ⅱ probes demonstrated superior water sensitivity and quenching stability.ACQ1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of incubation.Theoretical calculations verified that molecular planarity is more important than hydrophobicity for ACQ properties.Additionally,in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1,in contrast to 15% for P2.
基金Mae Fah Luang University is acknowledged for facilities and financially supported in partfunded by Thailand Graduate Institute of Science and Technology(TGIST),National Science and Technology De-velopment Agency(NSTDA),Thailand(Project No.SCA-CO-2558-1026-TH)
文摘Hyaluronic acid(HA, 20–50 kDa) is a hydrophilic macromolecule with anti-wrinkle effects and moisturizing properties. However, its high molecular weight prevents it from penetrating into the deeper layers of the skin and, thus, limits its benefits to topical effects. Thus, the objective of this study is to prepare nanoparticles of quaternized cyclodextrin-grafted chitosan(QCD-g-CS) associated with HA in different molar ratios of QCD-g-CS and HA. The conjugation of the carboxylic moieties of HA and the amides of QCD-g-CS was confirmed by Fourier-transform infrared spectroscopy. Thus, the system was optimized to create nanoparticles with a small size(235.63 ± 21.89 nm), narrow polydispersity index(0.13 ± 0.02), and zeta potential of 16.07 ± 0.65 m V. The association efficiency and loading efficiency were determined by ultra-performance liquid chromatography as 86.77 ± 0.69% and 10.85 ± 0.09%, respectively. The spherical morphology of the obtained nanoparticles was confirmed by transmission electron microscopy. Moreover, the in-vitro hydrating ability was significantly higher( P < 0.001) than that of bulk HA(3.29 ± 0.41 and 1.71 ± 0.05 g water/g sample, respectively). The safety of these nanoparticles at concentrations in the range of 0.01–0.10 mg/ml was confirmed via tests on human skin fibroblasts. Together, these results demonstrate that the developed nanoparticles are promising for future applications in cosmetics.
基金support from the Maximizing Investigators'Research Awards(R35GM119679,USA)and(R35GM144117,USA)from the National Institute of General Medical Sciences。
文摘Messenger RNA(mRNA)has drawn much attention in the medical field.Through various treatment approaches including protein replacement therapies,gene editing,and cell engineering,mRNA is becoming a potential therapeutic strategy for cancers.However,delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake.Therefore,in addition to mRNA modification,efforts have been devoted to developing nanoparticles for mRNA delivery.In this review,we introduce four categories of nanoparticle platform systems:lipid,polymer,lipid-polymer hybrid,and protein/peptide-mediated nanoparticles,together with their roles in facilitating mRNA-based cancer immunotherapies.We also highlight promising treatment regimens and their clinical translation.
基金The financial support from the National Natural Science Foundation of China(Nos.22201276,22131010,52021002)the Fundamental Research Funds for the Central Universities(No.WK2060000012)is gratefully acknowledged.
文摘Cyclic polymers are a class of polymers that feature endless topology,and the synthesis of cyclic polymers has attracted the attention of many researchers.Herein,cyclic polymers were efficiently constructed by self-folding cyclization technique at high concentrations.Linear poly((oligo(ethylene glycol)acrylate)-co-(dodecyl acrylate))(P(OEGA-co-DDA))precursors with different ratios of hydrophilic and hydrophobic moieties were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization using a bifunctional chain transfer agent with two anthryl end groups.The amphiphilic linear precursors underwent the self-folding process to generate polymeric nanoparticles in water.By irradiating the aqueous solution of the nanoparticles with 365 nm UV light,cyclic polymers were synthesized successfully via coupling of anthryl groups.The effects of the ratios of hydrophilic and hydrophobic moieties in linear P(OEGA-co-DDA)copolymers and polymer concentration on the purity of the obtained cyclic polymers were explored in detail via ^(1)H nuclear magnetic resonance(^(1)H NMR),dynamic light scattering(DLS),UV‒visible(vis)analysis,three-detection size exclusion chromatography(TD-SEC)and transmission electron microscopy(TEM).It was found that by adjusting the content of the hydrophilic segments in linear precursors,single chain polymeric nanoparticles(SCPNs)can be generated at high polymer concentrations.Therefore,cyclic polymers with high purity can be constructed efficiently.This method overcomes the limitation of traditional ring-closure method,which is typically conducted in highly dilute conditions,providing an efficient method for the scalable preparation of cyclic polymers.
基金the National Natural Science Foundation of China(51972056,52002061,52161145406)Shanghai Shuguang Program(18SG29)+2 种基金Program of Shanghai Academic/Technology Research Leader(20XD1420200)Major Science and Technology Innovation Project of Shandong Province(2019JZZY011108)Graduate Student Innovation Fund of Donghua University(CUSF-DH-D-2021010).
文摘Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ~80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t1/2 = 4.17 h) which is obviously longer than that (~0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H_(2)O_(2) into O_(2) to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.
基金supported by National Key Clinical Specialties Construction Programthe National Natural Science Foundation of China(No.81602699)the Sichuan Science and Technology program(No.2019YFG0266)。
文摘Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics,mainly including cancer diagnosis,controlled/triggered drug delivery,and real-time monitoring of therapeutic response.Particularly,tumor microenvironment(TME)-responsive polymeric nanocarriers in response to weak acidity,hypoxia,reactive oxygen species(ROS),glutathione(GSH),or tumor enzymes in the TME show great promise in facilitating tumor accumulation,enhancing tumor penetration,prolonging tumor retention,and achieving controlled drug release,thereby improving the efficiency of tumor therapy.Besides,the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors,which allows for the integration of the advantages of each treatment modality,addressing the shortcomings of the two methods,and amplifying the efficacy of tumor treatment while reducing adverse reactions.This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy,and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.
