Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarc...Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarcoma 180-bearing mice model through intraperitoneal （i.p.） administration. In vivo biodistribution was also investigated in Kunming mice bearing S180. Results demonstrated that the intraperitoneally injected DHA-NLC could significantly inhibit tumor growth at the dose levels of 20, 40 and 80 mg/kg, and their inhibition rates were 71.24%, 79.20% and 85.74%, respectively. The biodistribution of DHA after intraperitoneal injection of DHA-NLC in S180-bearing mice is remarkably different from the DHA solution. Therefore, DHA encapsulated in NLC does demonstrate superior anticancer effect to DHA suspension on S 180-bearing mice at the same dose and displayed a dose-dependent antitumor efficacy.展开更多
Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study ai...Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.展开更多
In this study, a novel technique for the preparation of 125I-5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FIAU） was developed, 125I-FIAU biodistribution profile was detected in Kunming mi...In this study, a novel technique for the preparation of 125I-5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FIAU） was developed, 125I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FTAU） was labeled with radioiodine （125I）. A rotary evaporation method was used to remove excess methanol. The reactant was purified through a Sep-Pak C18 reversal phase column. The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography （TLC）. The biodistribution of 125I-FIAU in Kunming mice was also detected. The results showed that 125I-FIAU could be radiolabeled effectively with FTAU, with mean labeling rate being （81±0.38）% （n =5）. The mean radiochemical purity of （98.01±0.40）% （n=5） was achieved after a reversal phase Sep-park column purification. 125I-FIAU was stable when incubated in normal human serum or in saline at 37°C, with a radiochemical purity 〉96% during a 0.5-24 h time period. Biological experiments exhibited rapid clearance of 125I-FIAU from the blood pool. 125I-FIAU was mostly excreted by kidneys. 125I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h. We were led to concluded that the new method of radioiodinization of FTAU for the preparation of 125I-FIAU is easy, highly effective and stable in vivo. The biodistribution of 125I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes.展开更多
AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical ima...AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.展开更多
Objective:To labelavidin(Av)or streptavidin(SA)with 153 Sm by takingadvantageof thehighbindingaffin-ityof biotinto Av or SA.Methods:A biotinderivative(DTPA-biotin)wasradiolabelledwith 153 Sm andthenboundto Av or SA.Th...Objective:To labelavidin(Av)or streptavidin(SA)with 153 Sm by takingadvantageof thehighbindingaffin-ityof biotinto Av or SA.Methods:A biotinderivative(DTPA-biotin)wasradiolabelledwith 153 Sm andthenboundto Av or SA.Thein vivo kineticsandbiodistributionof 153 Sm-labeledAv,SA andDTPA-biotinwerestudiedinratsandmice.Results:153 Sm-Avwascharacterizedby rapidclearancefromthebloodwithhighliverandrenaluptake;153 Sm-SAwas clearedfromthebloodslowlywithhighretentionintheliver,spleenandkidney,whereas 153 Sm-DTPA-biotinmetabolismwas accelerated,anditsexcretionwasmainlythroughthekidney.Conclu sion:Thebiodistributiondifferenceof SAandAvmay providean experimentalbasisfor theselectionof differentcomponentsof avidin-biotinsystemin pretagetingradioim-munoimagingandradioimmunotherapy.展开更多
Novel human interferon alpha 2b (hIFNα2b) muteins were developed by substituting cysteine residue (C) at positions 2 and 99 with aspartic acid residues (D). The mutein forms were then studied for pharmacokinetic prof...Novel human interferon alpha 2b (hIFNα2b) muteins were developed by substituting cysteine residue (C) at positions 2 and 99 with aspartic acid residues (D). The mutein forms were then studied for pharmacokinetic profile. In addition, the influence of charge on the protein structure was tested in vivo for the biodistribution pattern. Codon substitutions were performed by Polymerase Chain Reaction (PCR)-based site-directed mutagenesis on a previously constructed synthetic hIFNα2b open reading frame (ORF) cloned in pET32b expression plasmid. The result of nucleotide sequencing analysis confirmed that all codons were replaced successfully without any additional mutation. Three mutant forms of hIFNα2b ORF were overexpressed in Escherichia coli BL21 (DE3) resulted in three muteins: hIFNα2b C2D, hIFNα2b C99D, hIFNα2b C2D C99D. To follow the kinetic and localization of the mutein interferon after intravenous administration, Tc99m was used to label the proteins. In particular of elimination half-life, it was shown that hIFNα2b C2D C99D > hIFNα2bC2D > hIFNα2bC99D > wild type. hIFNα2b C2D C99D mutein showed highest blood accumulation after 30 minutes administration. Taken together, the charge of hIFNα2b seems to be responsible for the fate of hIFNα2b in vivo.展开更多
^(201)Tl-labeled Prussian blue and Au core@Prussian blue shell nanoparticles were synthesised and investigated in vivo as nanoprobes by using SPECT-CT scintigraphy.We demonstrate that the size,morphology and nanoparti...^(201)Tl-labeled Prussian blue and Au core@Prussian blue shell nanoparticles were synthesised and investigated in vivo as nanoprobes by using SPECT-CT scintigraphy.We demonstrate that the size,morphology and nanoparticle coating affect the kinetics of the nanoparticle biodistribution.展开更多
Upconversion nanoparticles(UCNPs)are emerging as highly promising nanomaterials due to their exceptional optical properties,enabling diverse applications in biosensing,bioimaging,photodynamic therapy,and drug delivery...Upconversion nanoparticles(UCNPs)are emerging as highly promising nanomaterials due to their exceptional optical properties,enabling diverse applications in biosensing,bioimaging,photodynamic therapy,and drug delivery.However,their potential toxicity should be comprehensively investigated for the safe utilization of UCNPs in several biomedical and environmental applications.This review systematically evaluates the current knowledge on UCNP toxicity from 2008 to 2024,focusing on key toxicological pathways,such as oxidative stress,reactive oxygen species(ROS)production,inflammatory responses,and apoptosis/necrosis,alongside their absorption,distribution,metabolism,and excretion processes and kinetics.Distinctively,this review introduces a bibliometric analysis of UCNP toxicity and biodistribution research,providing a quantitative assessment of publication trends,influential authors,leading institutions,funding agencies,and keyword occurrences.This approach offers a macroscopic perspective on the evolution and current landscape of UCNP safety research,a dimension largely unexplored in existing literature.Furthermore,the review combines mechanistic insights into UCNP toxicity with a critical evaluation of surface modifications,physicochemical properties,and administration routes,presenting a holistic framework for understanding UCNP biosafety.By combining bibliometric data with mechanistic insights,this review provides a data-driven perspective on UCNP-associated risks,actionable strategies for enhancing biosafety through surface engineering,and a forward-looking discussion on regulatory challenges and future directions for UCNP-based technologies.These findings bridge existing gaps in the literature and offer a comprehensive resource for researchers,clinicians,and policymakers,facilitating the safe development and utilization of UCNP-based technologies while establishing robust safety guidelines to mitigate adverse effects on human health and the environment.展开更多
Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples.Typically,these specimens are exposed to a panel of ...Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples.Typically,these specimens are exposed to a panel of labelled antibodies ex vivo,after sample collection.Here,we have developed a rhodium-labelled immunoconjugate of the HER2-targeted therapeutic IgG1 antibody,trastuzumab,and evaluated its in vivo biodistribution using mass cytometry techniques.A Rh^(3+)complex of a macrobicyclic sarcophagine(sar,3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane)chelator was appended with a dibromopyridazinedione(DBPD),to produce a novel disulfide bond labelling molecule,“Rh-sar-DBPD”.Rh-sar-DBPD was site-specifically conjugated to trastuzumab via its four native solvent-accessible disulfide bonds,to yield a near homogeneous,well-defined and stable pyridazinedione(PD)immunoconjugate,Rh-sar-PD-trastuzumab,in which four Rh-sar-PD groups were attached per molecule of trastuzumab.Inductively coupled plasma mass spectrometry(ICP-MS)and laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS)were then applied to measure ^(103)Rh content,as a proxy for Rh-sar-PD-trastuzumab accumulation,in in vitro and in vivo studies.ICP-MS in vitro studies indicated HER2-mediated uptake of Rh-sar-PD-trastuzumab in HER2-expressing breast cancer cells,with LA-ICP-MS images showing intercellular heterogeneity in Rh-sar-PD-trastuzumab uptake.To study the in vivo biodistribution of Rh-sar-PD-trastuzumab,female NSG mice bearing orthotopic HCC1954 breast cancer tumours were administered the immunoconjugate.Quantitative ICP-MS of ^(103)Rh signal in dissected tissues indicated receptor-specific HER2-mediated uptake in tumours,as well as accumulation in the spleen and liver.Finally,LA-ICP-MS imaging analysis of tumour and ovary tissue sections showed heterogeneous uptake in HER2-expressing HCC1954 tumour cells and follicular granulosa cells of the ovaries,which are known to express growth factor receptors.To the best of our knowledge,this is the first report in which both ICP-MS and LA-ICP-MS have been used on tissue exposed to a metal-tagged antibody in vivo,enabling quantification of the biodistribution of the novel immunoconjugate,Rh-sar-PD-trastuzumab,in a murine model of breast cancer.展开更多
The biological behavior of fullerene derivatives shows their considerable potential application in medicine field. To understand the biodistribution of C60 derivatives as drugs or drug carriers, a simple water-soluble...The biological behavior of fullerene derivatives shows their considerable potential application in medicine field. To understand the biodistribution of C60 derivatives as drugs or drug carriers, a simple water-soluble derivative C60(OH)x(O)y was labeled with 99mTc. A r-counter and a single photo emission computed tomography (SPECT) were used to assess the biodistribution and metabolism of the labeled compound in mice and rabbits, respectively. The results showed that the compound could be absorbed rapidly by tissues, especially by coronal bone, breastbone, backbone, extremity honeycomb, liver and spleen. The clearance was slow from all tissues except for brain. The compound might be excreted through urine and enteron. The biodistribution shows some difference from that of Yamago et al. In this note, we discuss the possible reason leading to the difference. Further study is needed to find out to what extent the C60 itself determines the biodistribution of derivatives.展开更多
Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly...Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly(vinylpyrrolidone)(PVP)-protected small Pd nanosheets(Pd-PVP) and some further surface-modified small Pd nanosheets such as Pd-PEG(SH) easily accumulated in reticuloendothelial system(RES) organs(liver, spleen, etc.) and were difficult to be cleared from these organs quickly. In the work, we surprisingly found that glutathione(GSH) could promote the clearance of surface-modified small Pd nanosheets(e.g. Pd-PVP, Pd-PEG(SH) and Pd-GSH) from the RES organs efficiently. The effects of GSH on the biodistribution and clearance of different surface-modified Pd nanosheets were investigated. Our results indicated that these surface-modified Pd nanosheets with or without GSH added caused no morbidity at target primary organs, and GSH can promote the clearance of different surface-modified Pd nanosheets in the order of Pd-PVP≈Pd-PEG(SH)>Pd-GSH. This study suggests that glutathione could be an attractive reagent for promoting nanomaterials eliminated from the reticuloendothelial systems(RES).展开更多
Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,...Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 hours.More recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research.Thereby,it potentially increases the radioimmunoimaging efficacy.However,there have been few studies with this antibody fragment.The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC xenografts.Methods Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was calculated.Similarly,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated.After injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 hours.Then the tumor/base ratios were calculated.Results ProGRP was highly expressed in NCI-H446 cells and xenograft tissue.The metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,respectively.The %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 hours.Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving optimal.Conclusion 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,indicating thatit could be a promising agent for SCLC radioimmunoimaging.展开更多
Background Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na1311 labe...Background Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na1311 labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis. Methods The 10-mer cyclic peptide contained the LyP-1 sequence （YCGNKRTRGC） was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na1311 using the chloramine-T method. The [1311] LyP-1 peptide and a [1311] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. Biodistribution and imaging results in vivo were obtained. Results The labeling efficiencies of LyP-1 peptide reached 80%＋5% （n=5）. The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37~C. In the biodistribution studies, the [1311] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [1311] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts. Conclusions The LyP-1 peptide could be effectively labeled with Na1311 and the labeled compound is stable in human serum at 37℃ for 24 hours. The high specificity of [1311] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.展开更多
Objective To synthesize18F labeled N-(2-18F-fluoropropionyl)-L-glutamine(18F-FPGLN)for tumor PET imaging,and to perform its biodistribution study on normal mice and PC-3 tumorbearing nude mice.Methods4-nitrophenyl-2-1...Objective To synthesize18F labeled N-(2-18F-fluoropropionyl)-L-glutamine(18F-FPGLN)for tumor PET imaging,and to perform its biodistribution study on normal mice and PC-3 tumorbearing nude mice.Methods4-nitrophenyl-2-18F-fluropropionate(18F-NFP)was synthesized on the MF-2V-IT-I synthesizer and was展开更多
Lipid nanoparticles(LNPs)have emerged as versatile carriers for the delivery of genetic medicines and small-molecule drugs,offering desired benefits for therapeutic applications.Optimization of the treatment efficacy ...Lipid nanoparticles(LNPs)have emerged as versatile carriers for the delivery of genetic medicines and small-molecule drugs,offering desired benefits for therapeutic applications.Optimization of the treatment efficacy of nanocarriers necessitates a thorough understanding of the connection between pharmacokinetics and physicochemical properties.This review consolidates scientific efforts to elucidate how LNP’s physicochemical attributes influence their in vivo fate,emphasizing particle size and shape,surface electric potential and ligand-binding chemistry.By examining the interplay between LNPs and biological barriers across various administration routes,this review provides insights into tailoring LNP properties for optimal delivery and reduced off-target effects.Recommendations for future research are provided to advance the study of LNP in vivo behaviors and offer a practical framework for optimizing in vivo performance through product design parameters.展开更多
Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which wa...Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.展开更多
The carbon quantum dots(CQDs)and their functionalized materials are promising in biomedical field because of their unique properties;meanwhile,a growing concern has been raised about the potential toxicity of these mo...The carbon quantum dots(CQDs)and their functionalized materials are promising in biomedical field because of their unique properties;meanwhile,a growing concern has been raised about the potential toxicity of these modified materials in biosystem.In this study,we synthesized original CQDs and two common functionalized CQDs including N-doped CQDs(NCQDs)and folic acid-modified CQDs(FACQDs),and compared the toxicity and biocompatibility with each other in vitro and in vivo.L929,C6 and normal cell MDCK were selected to detect the adverse reaction of these materials in vitro.No acute toxicity or obvious changes were noted from in vitro cytotoxicity studies with the dose of these CQD materials increasing to a high concentration at 1 mg/mL.Among these materials,the FA-CQDs show a much lower toxicity.Moreover,in vivo toxicity studies were performed on the nude mice for 15 days.The experimental animals in 10 or 15 mg/kg groups were similar with animals treated by phosphate buffer solution(PBS)after 15 days.The results of the multifa rious biochemical parameters also suggest that the functionalized products of CQDs do not influence the biological indicators at feasible concentration.Our findings in vitro and in vivo through toxicity tests demonstrate that CQDs and their modified materials are safe for future biological applications.展开更多
This review covers extensively the synthesis&surface modification,characterization,and application of magnetic nanoparticles.For biomedical applications,consideration should be given to factors such as design stra...This review covers extensively the synthesis&surface modification,characterization,and application of magnetic nanoparticles.For biomedical applications,consideration should be given to factors such as design strategies,the synthesis process,coating,and surface passivation.The synthesis method regulates post-synthetic change and specific applications in vitro and in vivo imaging/diagnosis and pharmacotherapy/administration.Special insights have been provided on biodistribution,pharmacokinetics,and toxicity in a living system,which is imperative for their wider application in biology.These nanoparticles can be decorated with multiple contrast agents and thus can also be used as a probe for multi-mode imaging or double/triple imaging,for example,MRI-CT,MRI-PET.Similarly loading with different drug molecules/dye/fluorescent molecules and integration with other carriers have found application not only in locating these particles in vivo but simultaneously target drug delivery/hyperthermia inside the body.Studies are underway to collect the potential of these magnetically driven nanoparticles in various scientific fields such as particle interaction,heat conduction,imaging,and magnetism.Surely,this comprehensive data will help in the further development of advanced techniques for theranostics based on high-performance magnetic nanoparticles and will lead this research area in a new sustainable direction.展开更多
DTPA was covalently conjugated to the copolymer of L lysine and L tyrosine, then transchelated with Gd EDTA,the resultant polymer chelates were further reacted with 6 O bromoacetyl D galacto...DTPA was covalently conjugated to the copolymer of L lysine and L tyrosine, then transchelated with Gd EDTA,the resultant polymer chelates were further reacted with 6 O bromoacetyl D galactose or methyl lactobionyloxyacetate to give PLT(Gd DTPA) with galactose moiety as liver targeting group.These macromolecular MRI contrast agents were characterized by means of FT IR, ICP AES, elementary analyses and UV Vis spectrophotometry. Their in vitro relaxivity and liver targeting property in mice were also investigated.展开更多
基金Fundamental Research Funds of Lanzhou University for the Central Universities (Grant No. lzujbky-2012-85)the Lanzhou Science and Technology Bureau (Grant No. 2012-2-80)
文摘Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarcoma 180-bearing mice model through intraperitoneal （i.p.） administration. In vivo biodistribution was also investigated in Kunming mice bearing S180. Results demonstrated that the intraperitoneally injected DHA-NLC could significantly inhibit tumor growth at the dose levels of 20, 40 and 80 mg/kg, and their inhibition rates were 71.24%, 79.20% and 85.74%, respectively. The biodistribution of DHA after intraperitoneal injection of DHA-NLC in S180-bearing mice is remarkably different from the DHA solution. Therefore, DHA encapsulated in NLC does demonstrate superior anticancer effect to DHA suspension on S 180-bearing mice at the same dose and displayed a dose-dependent antitumor efficacy.
基金the National Natural Science Foundation of China(Nos.81402640,81502816)the Natural Science Foundation of Hubei Province(No.2014CFB406)+1 种基金the Health and Family Planning Commission of Wuhan City(No.WX15B23)Training Plan for Young and Middleaged Backbone Talents in Wuhan[No.2014(77)].
文摘Biodistribution and toxicity assessment are critical for safe clinical use of newly developed medicines.Superparamagnetic iron oxide nanoparticles (SPION)are effective carriers for targeted drug delivery.This study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in vivo.SPION-PEI/siRNA complexes were prepared at different weight ratios.Cytotoxic effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA group.After a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the injection.Their distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian blue.The same organs were analyzed by H&E staining for any possible histopathological changes.Furthermore,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time points.Electrophoresis exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above 4.MTT assay showed that SPION-PEI loaded with siRNA had low cytotoxicity.In vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA deposition.The iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining gradually.No evidence was found of irreversible histopathological damage to any of the organs tested.These results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the target organs of SPION-PEI/siRNA complexes.SPION- PEI/siRNA may serve as in vivo carrier for biomedical medicines.
基金sponsored by the grants from the Scientific Research Foundation for the Returned Overseas Chinese Scholars of the Ministry of Education of China (No. [2008]890)the National Natural Science Foundation of China (Nos. 30872652, 30830041, 30772208)Fund of Doctoral Programs for New College Teachers of the Ministry of Education (No. 20070487160)
文摘In this study, a novel technique for the preparation of 125I-5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FIAU） was developed, 125I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FTAU） was labeled with radioiodine （125I）. A rotary evaporation method was used to remove excess methanol. The reactant was purified through a Sep-Pak C18 reversal phase column. The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography （TLC）. The biodistribution of 125I-FIAU in Kunming mice was also detected. The results showed that 125I-FIAU could be radiolabeled effectively with FTAU, with mean labeling rate being （81±0.38）% （n =5）. The mean radiochemical purity of （98.01±0.40）% （n=5） was achieved after a reversal phase Sep-park column purification. 125I-FIAU was stable when incubated in normal human serum or in saline at 37°C, with a radiochemical purity 〉96% during a 0.5-24 h time period. Biological experiments exhibited rapid clearance of 125I-FIAU from the blood pool. 125I-FIAU was mostly excreted by kidneys. 125I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h. We were led to concluded that the new method of radioiodinization of FTAU for the preparation of 125I-FIAU is easy, highly effective and stable in vivo. The biodistribution of 125I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes.
基金Supported by a grant(No.2016-7026)from the Asan Institute for Life Science,Seoul,Republic of Korea
文摘AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.
文摘Objective:To labelavidin(Av)or streptavidin(SA)with 153 Sm by takingadvantageof thehighbindingaffin-ityof biotinto Av or SA.Methods:A biotinderivative(DTPA-biotin)wasradiolabelledwith 153 Sm andthenboundto Av or SA.Thein vivo kineticsandbiodistributionof 153 Sm-labeledAv,SA andDTPA-biotinwerestudiedinratsandmice.Results:153 Sm-Avwascharacterizedby rapidclearancefromthebloodwithhighliverandrenaluptake;153 Sm-SAwas clearedfromthebloodslowlywithhighretentionintheliver,spleenandkidney,whereas 153 Sm-DTPA-biotinmetabolismwas accelerated,anditsexcretionwasmainlythroughthekidney.Conclu sion:Thebiodistributiondifferenceof SAandAvmay providean experimentalbasisfor theselectionof differentcomponentsof avidin-biotinsystemin pretagetingradioim-munoimagingandradioimmunotherapy.
文摘Novel human interferon alpha 2b (hIFNα2b) muteins were developed by substituting cysteine residue (C) at positions 2 and 99 with aspartic acid residues (D). The mutein forms were then studied for pharmacokinetic profile. In addition, the influence of charge on the protein structure was tested in vivo for the biodistribution pattern. Codon substitutions were performed by Polymerase Chain Reaction (PCR)-based site-directed mutagenesis on a previously constructed synthetic hIFNα2b open reading frame (ORF) cloned in pET32b expression plasmid. The result of nucleotide sequencing analysis confirmed that all codons were replaced successfully without any additional mutation. Three mutant forms of hIFNα2b ORF were overexpressed in Escherichia coli BL21 (DE3) resulted in three muteins: hIFNα2b C2D, hIFNα2b C99D, hIFNα2b C2D C99D. To follow the kinetic and localization of the mutein interferon after intravenous administration, Tc99m was used to label the proteins. In particular of elimination half-life, it was shown that hIFNα2b C2D C99D > hIFNα2bC2D > hIFNα2bC99D > wild type. hIFNα2b C2D C99D mutein showed highest blood accumulation after 30 minutes administration. Taken together, the charge of hIFNα2b seems to be responsible for the fate of hIFNα2b in vivo.
文摘^(201)Tl-labeled Prussian blue and Au core@Prussian blue shell nanoparticles were synthesised and investigated in vivo as nanoprobes by using SPECT-CT scintigraphy.We demonstrate that the size,morphology and nanoparticle coating affect the kinetics of the nanoparticle biodistribution.
基金sponsored by the National Natural Science Foundation of China(grant no.31971523)the Quanzhou Medical College Research Project(grant no.XYL2204)the Hospital Research Project of Shanghai Sixth People’s Hospital Fujian(grant no.2022JC03).
文摘Upconversion nanoparticles(UCNPs)are emerging as highly promising nanomaterials due to their exceptional optical properties,enabling diverse applications in biosensing,bioimaging,photodynamic therapy,and drug delivery.However,their potential toxicity should be comprehensively investigated for the safe utilization of UCNPs in several biomedical and environmental applications.This review systematically evaluates the current knowledge on UCNP toxicity from 2008 to 2024,focusing on key toxicological pathways,such as oxidative stress,reactive oxygen species(ROS)production,inflammatory responses,and apoptosis/necrosis,alongside their absorption,distribution,metabolism,and excretion processes and kinetics.Distinctively,this review introduces a bibliometric analysis of UCNP toxicity and biodistribution research,providing a quantitative assessment of publication trends,influential authors,leading institutions,funding agencies,and keyword occurrences.This approach offers a macroscopic perspective on the evolution and current landscape of UCNP safety research,a dimension largely unexplored in existing literature.Furthermore,the review combines mechanistic insights into UCNP toxicity with a critical evaluation of surface modifications,physicochemical properties,and administration routes,presenting a holistic framework for understanding UCNP biosafety.By combining bibliometric data with mechanistic insights,this review provides a data-driven perspective on UCNP-associated risks,actionable strategies for enhancing biosafety through surface engineering,and a forward-looking discussion on regulatory challenges and future directions for UCNP-based technologies.These findings bridge existing gaps in the literature and offer a comprehensive resource for researchers,clinicians,and policymakers,facilitating the safe development and utilization of UCNP-based technologies while establishing robust safety guidelines to mitigate adverse effects on human health and the environment.
基金CRUK for a Cancer Research UK Career Establishment Award(C63178/A24959)the EPSRC(EP/S032789/1,EP/T517793/1 and EP/S022104/1)the Wellcome Trust(212885/Z/18/Z)。
文摘Mass cytometry with antibodies labelled with stable metal isotopes enables both sensitive imaging and the quantification of protein expression in biological samples.Typically,these specimens are exposed to a panel of labelled antibodies ex vivo,after sample collection.Here,we have developed a rhodium-labelled immunoconjugate of the HER2-targeted therapeutic IgG1 antibody,trastuzumab,and evaluated its in vivo biodistribution using mass cytometry techniques.A Rh^(3+)complex of a macrobicyclic sarcophagine(sar,3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane)chelator was appended with a dibromopyridazinedione(DBPD),to produce a novel disulfide bond labelling molecule,“Rh-sar-DBPD”.Rh-sar-DBPD was site-specifically conjugated to trastuzumab via its four native solvent-accessible disulfide bonds,to yield a near homogeneous,well-defined and stable pyridazinedione(PD)immunoconjugate,Rh-sar-PD-trastuzumab,in which four Rh-sar-PD groups were attached per molecule of trastuzumab.Inductively coupled plasma mass spectrometry(ICP-MS)and laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS)were then applied to measure ^(103)Rh content,as a proxy for Rh-sar-PD-trastuzumab accumulation,in in vitro and in vivo studies.ICP-MS in vitro studies indicated HER2-mediated uptake of Rh-sar-PD-trastuzumab in HER2-expressing breast cancer cells,with LA-ICP-MS images showing intercellular heterogeneity in Rh-sar-PD-trastuzumab uptake.To study the in vivo biodistribution of Rh-sar-PD-trastuzumab,female NSG mice bearing orthotopic HCC1954 breast cancer tumours were administered the immunoconjugate.Quantitative ICP-MS of ^(103)Rh signal in dissected tissues indicated receptor-specific HER2-mediated uptake in tumours,as well as accumulation in the spleen and liver.Finally,LA-ICP-MS imaging analysis of tumour and ovary tissue sections showed heterogeneous uptake in HER2-expressing HCC1954 tumour cells and follicular granulosa cells of the ovaries,which are known to express growth factor receptors.To the best of our knowledge,this is the first report in which both ICP-MS and LA-ICP-MS have been used on tissue exposed to a metal-tagged antibody in vivo,enabling quantification of the biodistribution of the novel immunoconjugate,Rh-sar-PD-trastuzumab,in a murine model of breast cancer.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 19975066).
文摘The biological behavior of fullerene derivatives shows their considerable potential application in medicine field. To understand the biodistribution of C60 derivatives as drugs or drug carriers, a simple water-soluble derivative C60(OH)x(O)y was labeled with 99mTc. A r-counter and a single photo emission computed tomography (SPECT) were used to assess the biodistribution and metabolism of the labeled compound in mice and rabbits, respectively. The results showed that the compound could be absorbed rapidly by tissues, especially by coronal bone, breastbone, backbone, extremity honeycomb, liver and spleen. The clearance was slow from all tissues except for brain. The compound might be excreted through urine and enteron. The biodistribution shows some difference from that of Yamago et al. In this note, we discuss the possible reason leading to the difference. Further study is needed to find out to what extent the C60 itself determines the biodistribution of derivatives.
基金supported by the National Natural Science Foundation of China(21101131)the National Basic Research Program of China(2014CB932004)+2 种基金the Natural Science Foundation of Fujian Province(2012J01056)the Fundamental Research Funds for the Central Universities(2010121015)the open project grant from State Key Laboratory of Chemo/biosensing and Chemometrics(2013009)
文摘Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly(vinylpyrrolidone)(PVP)-protected small Pd nanosheets(Pd-PVP) and some further surface-modified small Pd nanosheets such as Pd-PEG(SH) easily accumulated in reticuloendothelial system(RES) organs(liver, spleen, etc.) and were difficult to be cleared from these organs quickly. In the work, we surprisingly found that glutathione(GSH) could promote the clearance of surface-modified small Pd nanosheets(e.g. Pd-PVP, Pd-PEG(SH) and Pd-GSH) from the RES organs efficiently. The effects of GSH on the biodistribution and clearance of different surface-modified Pd nanosheets were investigated. Our results indicated that these surface-modified Pd nanosheets with or without GSH added caused no morbidity at target primary organs, and GSH can promote the clearance of different surface-modified Pd nanosheets in the order of Pd-PVP≈Pd-PEG(SH)>Pd-GSH. This study suggests that glutathione could be an attractive reagent for promoting nanomaterials eliminated from the reticuloendothelial systems(RES).
文摘Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 hours.More recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research.Thereby,it potentially increases the radioimmunoimaging efficacy.However,there have been few studies with this antibody fragment.The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC xenografts.Methods Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was calculated.Similarly,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated.After injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 hours.Then the tumor/base ratios were calculated.Results ProGRP was highly expressed in NCI-H446 cells and xenograft tissue.The metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,respectively.The %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 hours.Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving optimal.Conclusion 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,indicating thatit could be a promising agent for SCLC radioimmunoimaging.
文摘Background Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na1311 labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis. Methods The 10-mer cyclic peptide contained the LyP-1 sequence （YCGNKRTRGC） was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na1311 using the chloramine-T method. The [1311] LyP-1 peptide and a [1311] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. Biodistribution and imaging results in vivo were obtained. Results The labeling efficiencies of LyP-1 peptide reached 80%＋5% （n=5）. The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37~C. In the biodistribution studies, the [1311] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [1311] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts. Conclusions The LyP-1 peptide could be effectively labeled with Na1311 and the labeled compound is stable in human serum at 37℃ for 24 hours. The high specificity of [1311] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.
文摘Objective To synthesize18F labeled N-(2-18F-fluoropropionyl)-L-glutamine(18F-FPGLN)for tumor PET imaging,and to perform its biodistribution study on normal mice and PC-3 tumorbearing nude mice.Methods4-nitrophenyl-2-18F-fluropropionate(18F-NFP)was synthesized on the MF-2V-IT-I synthesizer and was
文摘Lipid nanoparticles(LNPs)have emerged as versatile carriers for the delivery of genetic medicines and small-molecule drugs,offering desired benefits for therapeutic applications.Optimization of the treatment efficacy of nanocarriers necessitates a thorough understanding of the connection between pharmacokinetics and physicochemical properties.This review consolidates scientific efforts to elucidate how LNP’s physicochemical attributes influence their in vivo fate,emphasizing particle size and shape,surface electric potential and ligand-binding chemistry.By examining the interplay between LNPs and biological barriers across various administration routes,this review provides insights into tailoring LNP properties for optimal delivery and reduced off-target effects.Recommendations for future research are provided to advance the study of LNP in vivo behaviors and offer a practical framework for optimizing in vivo performance through product design parameters.
文摘Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.
基金financial support from the National Natural Science Foundation of China(Nos.81970985,81771122,81601613,21501123)Science&Technology Support Program of Sichuan Province(Nos.2018SZ0037,19YYJC2625)+2 种基金the Graduate Student’s Research and Innovation Fund of Sichuan University(No.2018YJSY108)the China Postdoctoral Science Foundation Funded Project(No.2018M640931)the Science&Technology Key Research and Development Program of Sichuan Province(No.2019YFS0142)。
文摘The carbon quantum dots(CQDs)and their functionalized materials are promising in biomedical field because of their unique properties;meanwhile,a growing concern has been raised about the potential toxicity of these modified materials in biosystem.In this study,we synthesized original CQDs and two common functionalized CQDs including N-doped CQDs(NCQDs)and folic acid-modified CQDs(FACQDs),and compared the toxicity and biocompatibility with each other in vitro and in vivo.L929,C6 and normal cell MDCK were selected to detect the adverse reaction of these materials in vitro.No acute toxicity or obvious changes were noted from in vitro cytotoxicity studies with the dose of these CQD materials increasing to a high concentration at 1 mg/mL.Among these materials,the FA-CQDs show a much lower toxicity.Moreover,in vivo toxicity studies were performed on the nude mice for 15 days.The experimental animals in 10 or 15 mg/kg groups were similar with animals treated by phosphate buffer solution(PBS)after 15 days.The results of the multifa rious biochemical parameters also suggest that the functionalized products of CQDs do not influence the biological indicators at feasible concentration.Our findings in vitro and in vivo through toxicity tests demonstrate that CQDs and their modified materials are safe for future biological applications.
基金Parveen Kumar acknowledges the department of science and technology(DST)New Delhi for the INSPIRE(Innovation in Science Pursuit for Inspired Research)-Faculty grant.
文摘This review covers extensively the synthesis&surface modification,characterization,and application of magnetic nanoparticles.For biomedical applications,consideration should be given to factors such as design strategies,the synthesis process,coating,and surface passivation.The synthesis method regulates post-synthetic change and specific applications in vitro and in vivo imaging/diagnosis and pharmacotherapy/administration.Special insights have been provided on biodistribution,pharmacokinetics,and toxicity in a living system,which is imperative for their wider application in biology.These nanoparticles can be decorated with multiple contrast agents and thus can also be used as a probe for multi-mode imaging or double/triple imaging,for example,MRI-CT,MRI-PET.Similarly loading with different drug molecules/dye/fluorescent molecules and integration with other carriers have found application not only in locating these particles in vivo but simultaneously target drug delivery/hyperthermia inside the body.Studies are underway to collect the potential of these magnetically driven nanoparticles in various scientific fields such as particle interaction,heat conduction,imaging,and magnetism.Surely,this comprehensive data will help in the further development of advanced techniques for theranostics based on high-performance magnetic nanoparticles and will lead this research area in a new sustainable direction.
文摘DTPA was covalently conjugated to the copolymer of L lysine and L tyrosine, then transchelated with Gd EDTA,the resultant polymer chelates were further reacted with 6 O bromoacetyl D galactose or methyl lactobionyloxyacetate to give PLT(Gd DTPA) with galactose moiety as liver targeting group.These macromolecular MRI contrast agents were characterized by means of FT IR, ICP AES, elementary analyses and UV Vis spectrophotometry. Their in vitro relaxivity and liver targeting property in mice were also investigated.
