Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of ...Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of innovative treatment strategies is of paramount importance for the management of diabetic wounds.Stemmed from the pleiotropic physicochemical properties of ferrocene and spermidine,this essay reported the ferrocene-spermidine co-polymer(Fc S)for the first time through facile amidation reaction.Molecular dynamics simulation revealed its self-assembly through hydrogen bonds,van der Waals forces instead of traditional nanoprecipitation.The self-assembled nanoparticles were demonstrated to exhibit great antioxidant property on cells to facilitate their migration and angiogenesis.Moreover,the integration with photocuring hydrogel,gelatin methacrylate(Gel MA),to construct Fc S nanoparticles loaded wound dressing(Gel MA@Fc S)further confirmed the potential on promoting diabetic wound enclosure through enhancement of re-epithelization and collagen deposition.Together with its great biocompatibility and biosafety,Gel MA@Fc S is expected to be developed into a wound dressing for clinical diabetic wounds management.展开更多
Photoswitchable fluorescent polymeric nanoparticles were widely concerned because of their excellent features including the flexible design,easy preparation and functionalization,and thus exhibited great application p...Photoswitchable fluorescent polymeric nanoparticles were widely concerned because of their excellent features including the flexible design,easy preparation and functionalization,and thus exhibited great application potential in information encryption,anti-counterfeiting,but remained challenging in improving the security.Herein,we described a self-erased time-resolved information encryption via using photoswitchable dual-color fluorescent polymeric nanoparticles(PDFPNs)containing two fluorescence dyes(blue and red)and photochromic spiroxazine derivatives.In view of the different thermo-induced isomerization rates of photochromic spiroxazine derivatives in different flexible substrates,the decoloration rate of PDFPNs can be programmatically tuned by regulating ratio between rigid polymer and flexible polymer.Therefore,after ultraviolet light(UV)irradiation,correct information could only be recognized in preestablished time during the self-erased process.Our results indicated that PDFPNs exhibited fast photo-responsibility(2 min),high fluorescence contrast,well-pleasing photo-reversibility(>20 times),and programmable thermo-responsiveness(24 s-6 h).We thus demonstrated their application in the selferased time-resolved information encryption and anti-counterfeiting with high security.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
With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the ba...With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the bacteria are extremely recalcitrant to the conventional antibiotic regimens.To address the emergence of MDR and biofilm-associated infections,numerous polymer-based materials have been designed and prepared recently.The subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens,to prevent the formation of biofilms,or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing biofilms.The advantages and shortcomings of these polymer-based materials are discussed,as well as the challenges we are facing in the clinical translation of these systems.展开更多
Herein, we report self-assembly of tadpole-like single chain polymeric nanoparticles （TPPs） and the ultrasonic response of the resultant superparticles. The TPPs are with an intramolecularly crosslinked poly（2-（me...Herein, we report self-assembly of tadpole-like single chain polymeric nanoparticles （TPPs） and the ultrasonic response of the resultant superparticles. The TPPs are with an intramolecularly crosslinked poly（2-（methacryloyloxy）ethyl pent-4-ynoate）-rpoly（hydroxyethyl methacrylate） （PMAEP-r-PHEMA） chain as the ＂head＂ and a poly（2- （dimethylamino）ethyl methacrylate （PDMAEMA） linear chain as the ＂tail＂, and are pre- pared simply and emciently by Glaser-coupling of the pendant alkynes in the PMAEP-r- PHEMA block in the common solvent methanol. The formation of the TPPs was confirmed by gel permeation chromatograph, nuclear magnetic resonance spectroscopy, dynamic light scattering, static dynamic scattering, and transmission electron microscopy. In aqueous solution, the amphiphilic TPPs could self-assemble into regular superparticles, driven by aggregation of the hydrophobic ＂heads＂. Since in the structure there is no chain entanglement and the embedding of PDMAEMA chains disturb close-packing of the ＂heads＂, the superpartieles are responsive to a low-energy ultrasonic vibration, as evidenced by greatly enhanced release of the functional molecules from the superparticles by treatment of a low-energy ultrasound. Therefore, the superparticles should be very promising in the use as the drug carriers that can be manipulated from a long distance, considering that ultrasonic energy can be focused at a small area in a relatively long distance from the ultrasound-radiating source.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
Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA...Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA-PMDNPs)consisting of poly-L-lysine(PLL)and poly glutamic-conjugated PTX/GEM(PGA-PTX and PGA-GEM)for FA receptor-targeted synergistic breast cancer therapy.The carboxyl-rich structure of PGA provided plenty reaction sites and negative charge for drug loading.Transmission electron microscopy(TEM)results showed that FA-PMDNPs had uniform particle size and spherical morphology.The hemolysis study proved that FA-PMDNPs had good biocompatibility.In vitro cell viability and in vivo studies showed that FA-PMDNPs more effectively inhibited the proliferation of FA receptor(FR)-overexpressing breast cancer cells(4T1)than the pure drugs.Consequently,these results demonstrated that FA-PMDNPs could be effectively targeted at cancer cells compared with free drugs,indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.展开更多
The primary aim of the study was to prepare narrow sized polymeric nanoparticles by implementing few modifications to the conventional nanoprecipitation technique and to evaluate the effect of various process paramete...The primary aim of the study was to prepare narrow sized polymeric nanoparticles by implementing few modifications to the conventional nanoprecipitation technique and to evaluate the effect of various process parameters on prepared polymeric nanoparticles.Eudragit E 100 nanoparticles were prepared by modified nanoprecipitation technique and step-by-step optimization was carried out to evaluate the effect of various process parameters such as organic solvent,polymer concentration,percentage of organic solvent,mode of addition of organic solvent in to aqueous phase,volume of aqueous phase,poloxamer 188 concentration,β-cyclodextrin concentration,temperature generated during sonication process,sonication duration,and drug concentration on the particle size,surface area,distribution width and uniformity of the prepared nanoparticles.The optimized process parameters were implemented to fabricate dual drug loaded Eudragit E 100 nanoparticles which were spherical in shape with mean particle size in the range of 118 to 140 nm,polydispersity index in the range of 0.187 to 0.254 and zeta potential in the range of 16.6 to 28.8 mV.Thus developed modified nanoprecipitation method can be used to fabricate narrow sized polymeric nanoparticles.展开更多
Dye-loaded polymeric nanoparticles(NPs)are promising bioimaging agents because of their available surface chemistry,high brightness,and tunable optical properties.However,high dye loadings can cause the aggregation-ca...Dye-loaded polymeric nanoparticles(NPs)are promising bioimaging agents because of their available surface chemistry,high brightness,and tunable optical properties.However,high dye loadings can cause the aggregation-caused quenching(ACQ)of the encapsulated fluorophores.Previously,we proposed to mitigate the ACQ inside polymeric NPs by insulating cationic dyes with bulky hydrophobic counterions.In order to implement new functionalities into dye-loaded NPs,here,we extend the concept of bulky counterions to anionic lanthanide-based complexes.We show that by employing Gd-based counterions with octadecyl rhodamine B loaded NPs at 30 wt% versus polymer,the fluorescence quantum yield can be increased to 10-fold(to 0.34).Moreover,Gd-anion provides NPs with enhanced contrast in electron microscopy.A combination of a luminescent Eu-based counterion with a far-red to near-infrared cyanine 5 dye(DiD)yields Forster resonance energy transfer NPs,where the UV-excited Eu-based counterion transfers energy to DiD,generating delayed fluorescence and large stokes shift of -340 nm.Cellular studies reveal low cytotoxicity of NPs and their capacity to internalize without detectable dye leakage,in contrast to leaky NPs with small counterions.Our findings show that the aggregation behavior of cationic dyes in the polymeric NPs can be controlled by bulky lanthanide anions,which will help in developing bright luminescent multifunctional nanomaterials.展开更多
The aim of this study was to develop and characterize methotrexate-loaded polymeric nanoparticles by nanoprecipitation technique.Eudragit■S 100 and ethyl cellulose were employed to develop methotrexate-loaded nanopar...The aim of this study was to develop and characterize methotrexate-loaded polymeric nanoparticles by nanoprecipitation technique.Eudragit■S 100 and ethyl cellulose were employed to develop methotrexate-loaded nanoparticles by nanoprecipitation technique.Six different formulations(f1,f2,f3,f4,f5 and f6)were prepared with each polymer by varying the drug to polymer ratios(1:1,1:1.5,1:2,1:3,1.5:1 and 2:1).Dimethyl sulfoxide(DMSO)was used as a solvent and Tween■20 as a surfactant.Among the six formulations of polymeric nanoparticles prepared by nanoprecipitation technique,F4 formulation was considered as a best formulation with each polymer.Based on comparison results of mean particle diameter,zeta potential,drug content and entrapment efficiency,Eudragit■S 100 was considered to be the most suitable polymer for preparation of methotrexate-loaded nanoparticles by nanoprecipitation technique.Based upon the evaluation studies,the best formulation was characterized for scanning electron microscopy(SEM),particle size,zeta potential and anti-cancer activity in MCF-7 cell line by MTT assay.展开更多
Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines ha...Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs,such as low water solubility and bioavailability,high toxicity,etc.However,it remains a significant challenge in encapsulating two drugs in a nanoparticle.To address this issue,computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading.Based on the sequential nanoprecipitation technology,five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles,and then screened 176 formulations under different experimental conditions.Based on these experimental data,machine learning methods are applied to pin down the key factors.The implementation of this methodology holds the potential to signif-icantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles,and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy.This approach provides a new strategy for enabling the streamlined,high-throughput screening and synthesis of new nanoscale drug-loaded entities.展开更多
Curcumin,a functional food polyphenol reported to inhibit cancer cell proliferation,invasion,angiogenesis and metastasis through interaction with multiple molecular targets.However,the clinical usefulness of curcumin ...Curcumin,a functional food polyphenol reported to inhibit cancer cell proliferation,invasion,angiogenesis and metastasis through interaction with multiple molecular targets.However,the clinical usefulness of curcumin in the treatment of cancer is limited due to poor solubility in water at acidic and neutral pH,hydrolytic degradation in alkaline pH and metabolism in the liver and intestine,resulting in decreased or absence of therapeutic efficacy.Hence,the present study was aimed to overcome the limitations of curcumin in the treatment of cancer by codelivery of nanosized curcumin and bioenhancer using acid degradable polymeric nanoparticles.Modified nanoprecipitation method was used to prepare void,curcumin-piperine,curcumin-quercetin and curcumin-silibinin encapsulated polymeric nanoparticles.Prepared nanoformulations were evaluated for particle size,polydispersity index,zeta potential,surface morphology,drug content,encapsulation efficiency,drug loading,in-vitro release,stability at elevated storage conditions,toxicity on normal liver cells,anticancer activity on various cancer cell lines and on cancer induced rats.Prepared curcumin-bioenhancer encapsulated polymeric nanoparticles were(a)spherical in shape with size<100 nm and displayed excellent uniformity;(b)showed>95%release of curcumin and bioenhancers within 45 minutes in gastric fluid;(c)proved non-toxic to normal liver cells;(d)extremely stable at elevated storage conditions;and(e)demonstrated enhanced anticancer activity against various cancer cell lines and mammary cancer in rats than the pure curcumin.Study concludes that the prepared curcumin-bioenhancer encapsulated polymeric nanoformulations significantly overcome the limitations of curcumin in the treatment of cancer and synergistically enhance its anticancer activity.However,out of three polymeric nanoformulations,curcumin-silibinin polymeric nanoformulation showed superior anticancer activity.展开更多
Melatonin is a natural hormone and with the advancement of age its production declines and thereby may result in some neurological disorders. Exogenous administration of melatonin has been suggested as a neuroprotecti...Melatonin is a natural hormone and with the advancement of age its production declines and thereby may result in some neurological disorders. Exogenous administration of melatonin has been suggested as a neuroprotective agent. Due to its low oral bioavailability, the loading of melatonin in polymeric nanoparticles could be an important tool to effectively use exogenous melatonin. The quantification of the incorporated drug within polymeric nanoparticles is an important step in nanoparticles characterization. An analytical method using high performance liquid chromatography equipped with photodiode array detector （HPLC-PDA） was developed and validated for melatonin determination in poly （lactic acid） nanoparticles obtained by a single emulsion-solvent evaporation technique. The melatonin in vitro release profile also was determined by the HPLC method. Mobile phase consisted of acetonitrile： water （65：35, v/v） pumped at a flow rate of 0.9 mL/min, in the isocratic mode and PDA detector was set at 220 nm. The method was validated in terms of the selectivity, linearity, precision, accuracy, robustness, limits of detection and quantification. Analytical curve was linear over the concentration range of 10-100 ~tg/mL, and limits of detection and quantification were 25.9 ng/mL and 78.7 ng/mL, respectively. The mean recovery for melatonin was 100.47% （RSD = 1.25%, n = 9）. In the intra- and inter- assay, the coefficient of variation was less than 2%. Robustness was proved performing changes in mobile phase, column temperature and flow rate. The method was suitable for the determination of melatonin encapsulation efficiency in poly（lactic acid） nanopartieles and for the evaluation of melatonin in vitro release profile.展开更多
Polymeric nanoparticles（NPs）have drawn great interest in the past few years due to their potential applications in the felds of biomedical and optical technologies.However,it is still a challenge to prepare function...Polymeric nanoparticles（NPs）have drawn great interest in the past few years due to their potential applications in the felds of biomedical and optical technologies.However,it is still a challenge to prepare functional polymeric NPs,especially for particle diameters smaller than 50 nm.In this work,we demonstrate a one-pot method to fabricate reactive poly（divinyl benzene-co-maleic anhydride）NPs（PDVBMAH NPs）through a self-stable precipitation polymerization process.The size and morphology of these PDVBMAH NPs were characterized in detail by scanning electronic microscopy,and their chemical structure was determined by IR.The results showed that these NPs were highly cross-linked and their diameter was about 30 nm with narrow distribution.Additionally,the DVB and MAH endow the NPs with reactive surface anhydride and pendant vinyl groups,and these particles could be further functionalized through reaction of these groups.A plausible pathway was proposed for the formation of PDVBMAH NPs.展开更多
<strong>Background: </strong>Recent decades witnessed a significant growth in terms of phytocompounds based therapeutics, extensively explored for almost all types of existing disorders. They have also bee...<strong>Background: </strong>Recent decades witnessed a significant growth in terms of phytocompounds based therapeutics, extensively explored for almost all types of existing disorders. They have also been widely investigated in Neurodegenerative disorders (NDDs) and Chlorogenic acid (CGA), a polyphenolic compound having potential anti-inflammatory and anti-oxidative properties, emerged as a promising compound in ameliorating NDDs. Owing to its poor stability, bioavailability and release kinetics, CGA needed a suitable nanocarrier based pharmaceutical design for targeting NDDs. <strong>Objective: </strong>The current study is aimed at the <em>in-silico</em> validation of CGA as an effective therapeutic agent targeting various NDDs followed by the fabrication of polymeric nanoparticles-based carrier system to overcome its pharmacological limitations and improve its stability. <strong>Methods:</strong> A successful <em>in-silico</em> validation using molecular docking techniques along with synthesis of CGA loaded polymeric nanoparticles (CGA-NPs) by ionic gelation method was performed. The statistical optimisation of the developed CGA-NPs was done by Box Behnken method and then the optimized formulation of CGA-NPs was characterised using particle size analysis (PSA), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (FTIR) along with in-vitro release kinetics analysis.<strong> Results & Conclusion:</strong> The results attained exhibited average particle size of 101.9 ± 1.5 nm, Polydispersibility (PDI) score of 0.065 and a ZP of <span style="white-space:nowrap;">−</span>17.4 mV. On a similar note, TEM results showed a size range of CGA-NPs between 90 - 110 nm with a spherical shape of NPs. Also, the data from in-vitro release kinetics showed a sustained release of CGA from the NPs following the first-order kinetics suggesting the appropriate designing of nanoformulation.展开更多
Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability wi...Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.展开更多
Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated ...Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.展开更多
Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This s...Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This study developed bifunctional oral lipid polymer hybrid nanoparticles(R8-PEG-PPNPs)that deliver superoxide dismutase(SOD)for the treatment of ulcerative colitis(UC).R8-PEG-PPNPs was composed of PCADK,PLGA,lecithin,and co-modified with stearic acid-octa-arginine and polyethylene glycol.The nanoparticles(NPs)are uniformly dispersed with a complete spherical structure.In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection.In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000µg/mL and promote cellular uptake.In experiments with ulcerative colitis mice,R8-PEG-PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation.Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs.展开更多
A pH-sensitive controlled release system was proposed in this work, which consists of mesoporous silica nanoparticles（MSNs） functionalized on the pore outlets with poly（4-vinylphenybronic acid-co-2-（dimethylamino...A pH-sensitive controlled release system was proposed in this work, which consists of mesoporous silica nanoparticles（MSNs） functionalized on the pore outlets with poly（4-vinylphenybronic acid-co-2-（dimethylamino）ethyl acrylate） [P（VPBA-DMAEA）]. Four kinds of P（VPBA-DMAEA）-gated MSNs were synthesized and applied for the p H-sensitive controlled release. The results showed that P（VPBADMAEA） can work as a p H-sensitive nanovalve. The release behavior of the hybrid nanoparticles could be adjusted by changing the mole ratio of VPBA and DMAEA. With the increasing of the mole ratio of VPBA,the leakage of the entrapped molecules in the pores of MSNs could be decreased at neutral and alkaline conditions. By altering the p H of buffer from 4.0 to 8.0, the valve could be switched ‘‘on＇＇ and ‘‘off＇＇reversibly. In addition, cells viability results indicated that these P（VPBA-DMAEA）-gated MSNs had good biocompatibility. We believe that these MSNs based p H-sensitive controlled release system will provide a promising nanodevice for sited release of drug delivery.展开更多
A novel method for the detection of PDGF-BB has been developed using double-strand DNA-copper nanoparticles （dsDNA-CuNPs） as fluorescent markers. This assay relies on the premise that the aptamer- based probe underg...A novel method for the detection of PDGF-BB has been developed using double-strand DNA-copper nanoparticles （dsDNA-CuNPs） as fluorescent markers. This assay relies on the premise that the aptamer- based probe undergoes a conformational change upon binding with target protein, and subsequently triggers polymerization reaction to generate dsDNA. Then, the resultant dsDNA can be used as a template for the formation of CuNPs with high fluorescence. Under the optimized conditions, the proposed assay allowed sensitive and selective detection of PDGF-BB with a detection limit of 4 nmol/L. This possibly makes it an attractive platform for the detection of a variety of biomolecules whose aptamers undergo similar conformational change.展开更多
基金supported by National Natural Science Foundation of China(Nos.52173150 and U22A20315)the Guangzhou Science and Technology Program City-University Joint Funding Project(No.2024A03J0604)+2 种基金the Science and Technology Program of Guangzhou(No.2024A03J0431)the start-up funding for the Seventh Affiliated Hospital of Sun Yat-sen University(Shenzhen)(No.ZSQYRSFPD0053)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515111126)。
文摘Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of innovative treatment strategies is of paramount importance for the management of diabetic wounds.Stemmed from the pleiotropic physicochemical properties of ferrocene and spermidine,this essay reported the ferrocene-spermidine co-polymer(Fc S)for the first time through facile amidation reaction.Molecular dynamics simulation revealed its self-assembly through hydrogen bonds,van der Waals forces instead of traditional nanoprecipitation.The self-assembled nanoparticles were demonstrated to exhibit great antioxidant property on cells to facilitate their migration and angiogenesis.Moreover,the integration with photocuring hydrogel,gelatin methacrylate(Gel MA),to construct Fc S nanoparticles loaded wound dressing(Gel MA@Fc S)further confirmed the potential on promoting diabetic wound enclosure through enhancement of re-epithelization and collagen deposition.Together with its great biocompatibility and biosafety,Gel MA@Fc S is expected to be developed into a wound dressing for clinical diabetic wounds management.
基金financially supported by the National Key R&D Program of China(Nos.2023YFB3812400,2023YFB3812403)National Natural Foundation of China(Nos.52273206,52350233)+1 种基金Hunan Provincial Natural Science Foundation(No.2021JJ10029)Huxiang High-level Talent Gathering Project(No.2022RC4039).
文摘Photoswitchable fluorescent polymeric nanoparticles were widely concerned because of their excellent features including the flexible design,easy preparation and functionalization,and thus exhibited great application potential in information encryption,anti-counterfeiting,but remained challenging in improving the security.Herein,we described a self-erased time-resolved information encryption via using photoswitchable dual-color fluorescent polymeric nanoparticles(PDFPNs)containing two fluorescence dyes(blue and red)and photochromic spiroxazine derivatives.In view of the different thermo-induced isomerization rates of photochromic spiroxazine derivatives in different flexible substrates,the decoloration rate of PDFPNs can be programmatically tuned by regulating ratio between rigid polymer and flexible polymer.Therefore,after ultraviolet light(UV)irradiation,correct information could only be recognized in preestablished time during the self-erased process.Our results indicated that PDFPNs exhibited fast photo-responsibility(2 min),high fluorescence contrast,well-pleasing photo-reversibility(>20 times),and programmable thermo-responsiveness(24 s-6 h).We thus demonstrated their application in the selferased time-resolved information encryption and anti-counterfeiting with high security.
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.
基金financially supported by the National Natural Science Foundation of China(Nos.21620102005,51933006,and 52003184)。
文摘With the emergence of multidrug resistance(MDR)in many pathogens,bacterial infections are becoming a growing threat to public health.The frightening scenario is due largely to the formation of biofilms,in which the bacteria are extremely recalcitrant to the conventional antibiotic regimens.To address the emergence of MDR and biofilm-associated infections,numerous polymer-based materials have been designed and prepared recently.The subject of this perspective is the recent development of polymer-based materials that have been applied to combat multidrug-resistant pathogens,to prevent the formation of biofilms,or enhance the eradication efficacy to mature biofilms via killing biofilm-bacteria or dispersing biofilms.The advantages and shortcomings of these polymer-based materials are discussed,as well as the challenges we are facing in the clinical translation of these systems.
基金This work was supported by the National Natural Science Foundation of China （No.21334001 and No.91127030）.
文摘Herein, we report self-assembly of tadpole-like single chain polymeric nanoparticles （TPPs） and the ultrasonic response of the resultant superparticles. The TPPs are with an intramolecularly crosslinked poly（2-（methacryloyloxy）ethyl pent-4-ynoate）-rpoly（hydroxyethyl methacrylate） （PMAEP-r-PHEMA） chain as the ＂head＂ and a poly（2- （dimethylamino）ethyl methacrylate （PDMAEMA） linear chain as the ＂tail＂, and are pre- pared simply and emciently by Glaser-coupling of the pendant alkynes in the PMAEP-r- PHEMA block in the common solvent methanol. The formation of the TPPs was confirmed by gel permeation chromatograph, nuclear magnetic resonance spectroscopy, dynamic light scattering, static dynamic scattering, and transmission electron microscopy. In aqueous solution, the amphiphilic TPPs could self-assemble into regular superparticles, driven by aggregation of the hydrophobic ＂heads＂. Since in the structure there is no chain entanglement and the embedding of PDMAEMA chains disturb close-packing of the ＂heads＂, the superpartieles are responsive to a low-energy ultrasonic vibration, as evidenced by greatly enhanced release of the functional molecules from the superparticles by treatment of a low-energy ultrasound. Therefore, the superparticles should be very promising in the use as the drug carriers that can be manipulated from a long distance, considering that ultrasonic energy can be focused at a small area in a relatively long distance from the ultrasound-radiating source.
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National Natural Science Foundation of China(Grant No.21877061)Natural Science Foundation of Jiangsu Province(Grant No.BK20171448)National and Local Joint Engineering Research Center of Biomedical Functional Materials。
文摘Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA-PMDNPs)consisting of poly-L-lysine(PLL)and poly glutamic-conjugated PTX/GEM(PGA-PTX and PGA-GEM)for FA receptor-targeted synergistic breast cancer therapy.The carboxyl-rich structure of PGA provided plenty reaction sites and negative charge for drug loading.Transmission electron microscopy(TEM)results showed that FA-PMDNPs had uniform particle size and spherical morphology.The hemolysis study proved that FA-PMDNPs had good biocompatibility.In vitro cell viability and in vivo studies showed that FA-PMDNPs more effectively inhibited the proliferation of FA receptor(FR)-overexpressing breast cancer cells(4T1)than the pure drugs.Consequently,these results demonstrated that FA-PMDNPs could be effectively targeted at cancer cells compared with free drugs,indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.
文摘The primary aim of the study was to prepare narrow sized polymeric nanoparticles by implementing few modifications to the conventional nanoprecipitation technique and to evaluate the effect of various process parameters on prepared polymeric nanoparticles.Eudragit E 100 nanoparticles were prepared by modified nanoprecipitation technique and step-by-step optimization was carried out to evaluate the effect of various process parameters such as organic solvent,polymer concentration,percentage of organic solvent,mode of addition of organic solvent in to aqueous phase,volume of aqueous phase,poloxamer 188 concentration,β-cyclodextrin concentration,temperature generated during sonication process,sonication duration,and drug concentration on the particle size,surface area,distribution width and uniformity of the prepared nanoparticles.The optimized process parameters were implemented to fabricate dual drug loaded Eudragit E 100 nanoparticles which were spherical in shape with mean particle size in the range of 118 to 140 nm,polydispersity index in the range of 0.187 to 0.254 and zeta potential in the range of 16.6 to 28.8 mV.Thus developed modified nanoprecipitation method can be used to fabricate narrow sized polymeric nanoparticles.
基金European Research Council ERC Consolidator grant Bright Sens,Grant/Award Number:648528。
文摘Dye-loaded polymeric nanoparticles(NPs)are promising bioimaging agents because of their available surface chemistry,high brightness,and tunable optical properties.However,high dye loadings can cause the aggregation-caused quenching(ACQ)of the encapsulated fluorophores.Previously,we proposed to mitigate the ACQ inside polymeric NPs by insulating cationic dyes with bulky hydrophobic counterions.In order to implement new functionalities into dye-loaded NPs,here,we extend the concept of bulky counterions to anionic lanthanide-based complexes.We show that by employing Gd-based counterions with octadecyl rhodamine B loaded NPs at 30 wt% versus polymer,the fluorescence quantum yield can be increased to 10-fold(to 0.34).Moreover,Gd-anion provides NPs with enhanced contrast in electron microscopy.A combination of a luminescent Eu-based counterion with a far-red to near-infrared cyanine 5 dye(DiD)yields Forster resonance energy transfer NPs,where the UV-excited Eu-based counterion transfers energy to DiD,generating delayed fluorescence and large stokes shift of -340 nm.Cellular studies reveal low cytotoxicity of NPs and their capacity to internalize without detectable dye leakage,in contrast to leaky NPs with small counterions.Our findings show that the aggregation behavior of cationic dyes in the polymeric NPs can be controlled by bulky lanthanide anions,which will help in developing bright luminescent multifunctional nanomaterials.
文摘The aim of this study was to develop and characterize methotrexate-loaded polymeric nanoparticles by nanoprecipitation technique.Eudragit■S 100 and ethyl cellulose were employed to develop methotrexate-loaded nanoparticles by nanoprecipitation technique.Six different formulations(f1,f2,f3,f4,f5 and f6)were prepared with each polymer by varying the drug to polymer ratios(1:1,1:1.5,1:2,1:3,1.5:1 and 2:1).Dimethyl sulfoxide(DMSO)was used as a solvent and Tween■20 as a surfactant.Among the six formulations of polymeric nanoparticles prepared by nanoprecipitation technique,F4 formulation was considered as a best formulation with each polymer.Based on comparison results of mean particle diameter,zeta potential,drug content and entrapment efficiency,Eudragit■S 100 was considered to be the most suitable polymer for preparation of methotrexate-loaded nanoparticles by nanoprecipitation technique.Based upon the evaluation studies,the best formulation was characterized for scanning electron microscopy(SEM),particle size,zeta potential and anti-cancer activity in MCF-7 cell line by MTT assay.
基金Australian National Health and Medical Research Council,Grant/Award Number:APP2008698Australian Research Council,Grant/Award Number:DE230101044。
文摘Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs,such as low water solubility and bioavailability,high toxicity,etc.However,it remains a significant challenge in encapsulating two drugs in a nanoparticle.To address this issue,computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading.Based on the sequential nanoprecipitation technology,five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles,and then screened 176 formulations under different experimental conditions.Based on these experimental data,machine learning methods are applied to pin down the key factors.The implementation of this methodology holds the potential to signif-icantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles,and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy.This approach provides a new strategy for enabling the streamlined,high-throughput screening and synthesis of new nanoscale drug-loaded entities.
文摘Curcumin,a functional food polyphenol reported to inhibit cancer cell proliferation,invasion,angiogenesis and metastasis through interaction with multiple molecular targets.However,the clinical usefulness of curcumin in the treatment of cancer is limited due to poor solubility in water at acidic and neutral pH,hydrolytic degradation in alkaline pH and metabolism in the liver and intestine,resulting in decreased or absence of therapeutic efficacy.Hence,the present study was aimed to overcome the limitations of curcumin in the treatment of cancer by codelivery of nanosized curcumin and bioenhancer using acid degradable polymeric nanoparticles.Modified nanoprecipitation method was used to prepare void,curcumin-piperine,curcumin-quercetin and curcumin-silibinin encapsulated polymeric nanoparticles.Prepared nanoformulations were evaluated for particle size,polydispersity index,zeta potential,surface morphology,drug content,encapsulation efficiency,drug loading,in-vitro release,stability at elevated storage conditions,toxicity on normal liver cells,anticancer activity on various cancer cell lines and on cancer induced rats.Prepared curcumin-bioenhancer encapsulated polymeric nanoparticles were(a)spherical in shape with size<100 nm and displayed excellent uniformity;(b)showed>95%release of curcumin and bioenhancers within 45 minutes in gastric fluid;(c)proved non-toxic to normal liver cells;(d)extremely stable at elevated storage conditions;and(e)demonstrated enhanced anticancer activity against various cancer cell lines and mammary cancer in rats than the pure curcumin.Study concludes that the prepared curcumin-bioenhancer encapsulated polymeric nanoformulations significantly overcome the limitations of curcumin in the treatment of cancer and synergistically enhance its anticancer activity.However,out of three polymeric nanoformulations,curcumin-silibinin polymeric nanoformulation showed superior anticancer activity.
基金supported by Comissao de Aperfeicoamento de Pessoal do Nível Superior(CAPES)in the form of scholarship for LGM
文摘Melatonin is a natural hormone and with the advancement of age its production declines and thereby may result in some neurological disorders. Exogenous administration of melatonin has been suggested as a neuroprotective agent. Due to its low oral bioavailability, the loading of melatonin in polymeric nanoparticles could be an important tool to effectively use exogenous melatonin. The quantification of the incorporated drug within polymeric nanoparticles is an important step in nanoparticles characterization. An analytical method using high performance liquid chromatography equipped with photodiode array detector （HPLC-PDA） was developed and validated for melatonin determination in poly （lactic acid） nanoparticles obtained by a single emulsion-solvent evaporation technique. The melatonin in vitro release profile also was determined by the HPLC method. Mobile phase consisted of acetonitrile： water （65：35, v/v） pumped at a flow rate of 0.9 mL/min, in the isocratic mode and PDA detector was set at 220 nm. The method was validated in terms of the selectivity, linearity, precision, accuracy, robustness, limits of detection and quantification. Analytical curve was linear over the concentration range of 10-100 ~tg/mL, and limits of detection and quantification were 25.9 ng/mL and 78.7 ng/mL, respectively. The mean recovery for melatonin was 100.47% （RSD = 1.25%, n = 9）. In the intra- and inter- assay, the coefficient of variation was less than 2%. Robustness was proved performing changes in mobile phase, column temperature and flow rate. The method was suitable for the determination of melatonin encapsulation efficiency in poly（lactic acid） nanopartieles and for the evaluation of melatonin in vitro release profile.
文摘Polymeric nanoparticles（NPs）have drawn great interest in the past few years due to their potential applications in the felds of biomedical and optical technologies.However,it is still a challenge to prepare functional polymeric NPs,especially for particle diameters smaller than 50 nm.In this work,we demonstrate a one-pot method to fabricate reactive poly（divinyl benzene-co-maleic anhydride）NPs（PDVBMAH NPs）through a self-stable precipitation polymerization process.The size and morphology of these PDVBMAH NPs were characterized in detail by scanning electronic microscopy,and their chemical structure was determined by IR.The results showed that these NPs were highly cross-linked and their diameter was about 30 nm with narrow distribution.Additionally,the DVB and MAH endow the NPs with reactive surface anhydride and pendant vinyl groups,and these particles could be further functionalized through reaction of these groups.A plausible pathway was proposed for the formation of PDVBMAH NPs.
文摘<strong>Background: </strong>Recent decades witnessed a significant growth in terms of phytocompounds based therapeutics, extensively explored for almost all types of existing disorders. They have also been widely investigated in Neurodegenerative disorders (NDDs) and Chlorogenic acid (CGA), a polyphenolic compound having potential anti-inflammatory and anti-oxidative properties, emerged as a promising compound in ameliorating NDDs. Owing to its poor stability, bioavailability and release kinetics, CGA needed a suitable nanocarrier based pharmaceutical design for targeting NDDs. <strong>Objective: </strong>The current study is aimed at the <em>in-silico</em> validation of CGA as an effective therapeutic agent targeting various NDDs followed by the fabrication of polymeric nanoparticles-based carrier system to overcome its pharmacological limitations and improve its stability. <strong>Methods:</strong> A successful <em>in-silico</em> validation using molecular docking techniques along with synthesis of CGA loaded polymeric nanoparticles (CGA-NPs) by ionic gelation method was performed. The statistical optimisation of the developed CGA-NPs was done by Box Behnken method and then the optimized formulation of CGA-NPs was characterised using particle size analysis (PSA), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (FTIR) along with in-vitro release kinetics analysis.<strong> Results & Conclusion:</strong> The results attained exhibited average particle size of 101.9 ± 1.5 nm, Polydispersibility (PDI) score of 0.065 and a ZP of <span style="white-space:nowrap;">−</span>17.4 mV. On a similar note, TEM results showed a size range of CGA-NPs between 90 - 110 nm with a spherical shape of NPs. Also, the data from in-vitro release kinetics showed a sustained release of CGA from the NPs following the first-order kinetics suggesting the appropriate designing of nanoformulation.
文摘Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.
基金supported by the National Natural Science Foundation of China(Grant Nos.61727823,51873160)the joint research project of Health and Education Commission of Fujian Province(Grant No.2019-WJ-20).
文摘Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.
基金the financial support received form National Natural Science Foundation of China(No.82073784)Jilin Province Science and Technology Development Program(No.20200801012GH)Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province(No.2019C050-4).
文摘Protein-based drugs have received extensive attention in the field of drug research in recent years.However,protein-based drug activity is difficult to maintain during oral delivery,which limits its application.This study developed bifunctional oral lipid polymer hybrid nanoparticles(R8-PEG-PPNPs)that deliver superoxide dismutase(SOD)for the treatment of ulcerative colitis(UC).R8-PEG-PPNPs was composed of PCADK,PLGA,lecithin,and co-modified with stearic acid-octa-arginine and polyethylene glycol.The nanoparticles(NPs)are uniformly dispersed with a complete spherical structure.In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection.In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000µg/mL and promote cellular uptake.In experiments with ulcerative colitis mice,R8-PEG-PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation.Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs.
基金supported by the National Natural Science Foundation of China (Nos. 21190040, 21175035, 21375034)National Basic Research Program of China (No. 2011CB911002)International Science & Technology Cooperation Program of China (No. 2010DFB30300)
文摘A pH-sensitive controlled release system was proposed in this work, which consists of mesoporous silica nanoparticles（MSNs） functionalized on the pore outlets with poly（4-vinylphenybronic acid-co-2-（dimethylamino）ethyl acrylate） [P（VPBA-DMAEA）]. Four kinds of P（VPBA-DMAEA）-gated MSNs were synthesized and applied for the p H-sensitive controlled release. The results showed that P（VPBADMAEA） can work as a p H-sensitive nanovalve. The release behavior of the hybrid nanoparticles could be adjusted by changing the mole ratio of VPBA and DMAEA. With the increasing of the mole ratio of VPBA,the leakage of the entrapped molecules in the pores of MSNs could be decreased at neutral and alkaline conditions. By altering the p H of buffer from 4.0 to 8.0, the valve could be switched ‘‘on＇＇ and ‘‘off＇＇reversibly. In addition, cells viability results indicated that these P（VPBA-DMAEA）-gated MSNs had good biocompatibility. We believe that these MSNs based p H-sensitive controlled release system will provide a promising nanodevice for sited release of drug delivery.
基金supported by the National Natural Science Foundation of China(Nos.21190041,21190044,21175035)National Basic Research Program(No.2011CB911002)Interna-tional Science&Technology operation Program of China(No.2010DFB30300)
文摘A novel method for the detection of PDGF-BB has been developed using double-strand DNA-copper nanoparticles （dsDNA-CuNPs） as fluorescent markers. This assay relies on the premise that the aptamer- based probe undergoes a conformational change upon binding with target protein, and subsequently triggers polymerization reaction to generate dsDNA. Then, the resultant dsDNA can be used as a template for the formation of CuNPs with high fluorescence. Under the optimized conditions, the proposed assay allowed sensitive and selective detection of PDGF-BB with a detection limit of 4 nmol/L. This possibly makes it an attractive platform for the detection of a variety of biomolecules whose aptamers undergo similar conformational change.
