We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast canc...We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast cancer cells which expressed redfluorescent protein(RFP).For FMT system,reflective illumination mode was adopted with full-angle data acquisition.[18F]-Fluorodeoxyglucose([18F]-FDG)was used as radioactive tracer for PET.Both data were acquired simultaneously and then reconstructed separately before fusion.Fluorescent tomography results showed exactly where the tumor was located while PET results offered more metabolic information.Results confirmed feasibility for tumor detection and showed superiority to single modality imaging.展开更多
The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as...The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as the core can significantly reduce the signal of Fe3O4@MnO2@PAA nanoparticles.MnO2 nanoshells can be decomposed into paramagnetic Mn2+under the acidic environment in the tumor,which enhanced the T1 signal.The pH-responsive T1/T2 dual-mode magnetic resonance imaging(MRI)contrast agent had good sensitivity and specificity,providing more comprehensive and detailed information for tumor diagnosis.In addition,Fe3O4@MnO2@PAA nanoparticles showed excellent absorption capacity in the near-infrared region(NIR),which could be used as a good photothermal conversion material to mediate photothermal treatment of tumors.Therefore,the pHresponsive dual-mode MRI nanoparticle-mediated photothermal therapy showed good application potential in tumor treatment and diagnosis.展开更多
A facile strategy to fabricate gold nanorod@polyacrylic acid/calcium phosphate(Au NR@-PAA/Ca P) yolk–shell nanoparticles(NPs) composed with a PAA/Ca P shell and an Au NR yolk is reported. The asobtained Au NR@PAA/Ca ...A facile strategy to fabricate gold nanorod@polyacrylic acid/calcium phosphate(Au NR@-PAA/Ca P) yolk–shell nanoparticles(NPs) composed with a PAA/Ca P shell and an Au NR yolk is reported. The asobtained Au NR@PAA/Ca P yolk–shell NPs possess ultrahigh doxorubicin(DOX) loading capability(1 mg DOX/mg NPs), superior photothermal conversion property(26%)and p H/near-infrared(NIR) dual-responsive drug delivery performance. The released DOX continuously increased due to the damage of the Ca P shell at low p H values. When the DOX-loaded Au NR@PAA/Ca P yolk–shell NPs wereexposed to NIR irradiation, a burst-like drug release occurs owing to the heat produced by the Au NRs. Furthermore,Au NR@PAA/Ca P yolk–shell NPs are successfully employed for synergic dual-mode X-ray computed tomography/photoacoustic imaging and chemo-photothermal cancer therapy. Therefore, this work brings new insights for the synthesis of multifunctional nanomaterials and extends theranostic applications.展开更多
AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents(NPCAs) for echographic medical imaging at low ultrasound(US) frequency. METHODS: We synthesized three differe...AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents(NPCAs) for echographic medical imaging at low ultrasound(US) frequency. METHODS: We synthesized three different nanosized structures:(1) Pure silica nanospheres(SiNSs);(2) FePt-iron oxide(FePt-IO)-coated SiNSs; and(3) IOcoated SiNSs, employing three different diameter of SiNS-core(160, 330 and 660 nm). Tissue mimicking phantoms made of agarose gel solution containing 5 mg of different NPCAs in 2 mL-Eppendorf tubes, were insonified by a commercial echographic system at three different low US pulse values(2.5, 3.5 and 4.5 MHz). The raw radiofrequency signal, backscattered from each considered NPCA containing sample, has been processed in order to calculate the US average backscatter intensity and compare the acoustic behavior of the different NPCA types. RESULTS: The highest US contrast was exhibited by pure SiNSs; FePt-IO-coated SiNSs acoustical behavior followed a similar trend of pure SiNSs with a slight difference in terms of brightness values. The acoustic response of the examined NPCAs resulted function of both SiNS diameter and US frequency. Specifically, higher US frequencies determined higher value of the backscatter for a given SiNS diameter. Frequencydependent enhancement was marked for pure SiNSs and became less remarkable for FePt-IO-coated SiNSs, whereas IO-coated SiNSs resulted almost unaffected by such frequency variations. Pure and FePt-IO-coated SiNSs evidenced an image backscatter increasing with the diameter up to 330 nm. Conversely, among the types of NPCA tested, IO-coated SiNSs showed the lowest acoustical response for each synthesized diameter and employed US frequency, although a diameter-dependent raising trend was evidenced. CONCLUSION: The US characterization of magnetically covered SiNS shows that FePt-IO, rather than IO, was the best magnetic coating for realizing NPCAs suitable for dual mode imaging of deep organs, combining US and magnetic resonance imaging.展开更多
The combination of near-infrared(NIR)fluorescence imaging(FLI)and photoacoustic imaging(PAI)can effectively compensate for each other’s inherent limitations,which can provide reliable and rich information on tumor bi...The combination of near-infrared(NIR)fluorescence imaging(FLI)and photoacoustic imaging(PAI)can effectively compensate for each other’s inherent limitations,which can provide reliable and rich information on tumor biology.Therefore,the development of FL/PA dual-modality imaging probes is beneficial for achieving precision cancer diagnosis and treatment.Herein,we designed an efficient phototherapy agent methoxy bithiophene indene(OTIC),which was based on aggregation-induced emission(AIE)active fluorophores.To improve the water dispersion and enrichment of OTIC at the tumor site,OTIC nanoparticles(OTIC NPs)were prepared by a nanoprecipitation method.The balance between radiation and non-radiation energy dissipation was regulated by the strong donor-acceptor interaction and intramolecular motion.So OTIC NPs exhibited bright NIR fluorescence,photoacoustic signals,efficient generation of reactive oxygen species,and high photothermal conversion efficiency under NIR irradiation.Accurate imaging of the tumor and mice sentinel lymph nodes(SLNs)with OTIC NPs was visualized by NIR FL/PA dual-modal imaging.With the comprehensive imaging information provided by OTIC NPs in vivo,tumors were ablated under laser irradiation,which greatly improved the therapeutic efficacy.OTIC NPs would be possible to realize the precise guidance of FL/PA imaging for tumor treatment in the future clinical application.展开更多
Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in s...Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in serving as pH-responsive T1-T2^*dual-modal magnetic resonance(MR)imaging contrast agents.The released Mn^2+shortened T1 relaxation time,meanwhile the superparamagnetic Fe3O4 enhanced T2 contrast imaging.The release rate of Mn ions reaches 31.66%under the condition of pH=5.0,which is similar to tumor microenvironment and organelles.Cytotoxicity assays show that MnSiO3@Fe3O4@C NPs have minor toxicity,even at high concentrations.After intravenous injection of MnSiO3@Fe3O4@C NPs,a rapid contrast enhancement in tumors was achieved with a significant enhancement of 132%after 24 h of the administration.Moreover,a significant decreasement of 53.8%was witnessed in T2 MR imaging signal.It demonstrated that MnSiO3@Fe3O4@C NPs can act as both positive and negative MR imaging contrast agents.Besides,owing to the pH-responsive degradation of mesoporous MnSiO3,MnSiO3@Fe3O4@C NPs can also be used as potential drug systems for cancer theranostics.展开更多
The prognosis of glioblastoma(GBM)remains challenging,primarily due to the lack of a precise,effective imaging technique for comprehensively characterization.Addressing GBM diagnostic challenges,our study introduces a...The prognosis of glioblastoma(GBM)remains challenging,primarily due to the lack of a precise,effective imaging technique for comprehensively characterization.Addressing GBM diagnostic challenges,our study introduces an innovative dual-modal imaging that merges near-infrared(NIR)fluorescent imaging with magnetic resonance imaging(MR).This method employs superparamagnetic iron oxide nanoparticies coated with NIR fluorescent dyes,specifically Cyanine 7,and targeted peptides.This synthetic probe facilitates MRI functionality through superparamagnetic iron oxide nanoparticles,provides NIR imaging capability via Cyanine 7 and enhances tumor targeting trough peptide interactions,offering a comprehensive diagnostic tool for GBM.Notably,the probe traverses the blood-brain barrier,targeting GBM in vivo via peptides,producing clear and discermible images in both modalities.Cytotoxicity and histopathology assessments confirm the probe's favorable safet profile.These findings suggest that the dual-modal MRINIR fluorescent imaging probe could revolutionize GBM prognosis and survival rate which can also be extended to other tumors type.展开更多
Taking apart in numerous physiological and pathological activities,hydrogen sulfide(H_(2)S)has been selected as an excellent target spot for the early diagnosis of cancer.So far,there are many mature probes that apply...Taking apart in numerous physiological and pathological activities,hydrogen sulfide(H_(2)S)has been selected as an excellent target spot for the early diagnosis of cancer.So far,there are many mature probes that apply single optical imaging to monitor endogenous H_(2)S.Nevertheless,a single modality is not an ideal method to afford accurate diagnostic information in comprehensive biological organisms.Herein,we developed a dual-modal imaging probe BWS.This designed probe showed a specific response to H_(2)S with both chemiluminescence and NIR fluorescence light-up.The concurrence of fluorescence and chemiluminescence signal provided“double insurances”for highly accurate monitoring of H_(2)S.Satisfactorily,this dual-modal imaging probe performed precise visualization of endogenous H_(2)S in living cells and in vivo.We envisaged that this chemiluminescence/fluorescence real-time dual-modality strategy for H_(2)S detection will expand and optimize the multimodal imaging methods for efficient diagnosis and treatment of cancer.展开更多
Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is...Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance.Herein,gadolinium-containing semiconductor polymer nanoparticles(SPN-Gd)were designed and prepared.The nanoparticles consist of a near-infrared(NIR)absorption semiconductor polymer(PCPDTBT)served as fluorescence signal source and a photothermal conversion agent(PTA)and a gadolinium-grafted triblock amphiphilic copolymer(F127-DTPA-Gd)served as a magnetic resonance imaging(MRI)contrast agent and nanocarrier.The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time,and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy(PTT).Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.展开更多
Nanoprobes that offer both fluorescence imaging(FI)and magnetic resonance imaging(MRI)can provide supplementary information and hold synergistic advantages.However,synthesis of such dual-modality imaging probes that s...Nanoprobes that offer both fluorescence imaging(FI)and magnetic resonance imaging(MRI)can provide supplementary information and hold synergistic advantages.However,synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups,high stability,great biocompatibility and desired dual-modality imaging results remains challenging.In this study,we used an amphiphilic block polymer from(ethylene glycol)methyl ether methacrylate(OEGMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)derivatives as a carrier to conjugate a MR contrast agent,Gd-DOTA,and a two-photon fluorophore with an aggregation-induced emission(AIE)effect,TPBP,to construct a MR/two-photon fluorescence dual-modality contrast agent,Gd-DOTA-TPBP.Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r_(1)value for Gd-DOTA-TPBP,revealing a great MR imaging resolution.The contrast agent specifically accumulated in the tumor region,allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging.Meanwhile,coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity,but also significantly enhanced its imaging performance in an aqueous phase.Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI.Since high-resolution,complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP,it has great potential in the early phase of disease diagnosis.展开更多
Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using i...Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms.Our study aimed to develop Au-Fe3O4 silica nanoparticles(NPs)as tracking nanoplatforms for dualmodal stem cell imaging.Methods:Au-Fe3O4 silica NPs were synthesized by seed-mediated growth method and co-precipitation.The efficiency and cytotoxicity of the NPslabeled bone marrow-derived mesenchymal stem cells(BMMSCs)were evaluated by Cell Counting Kit-8 assays,ICPMS,phenotypic characterization,and histological staining.The biodistribution of labeled BM-MSCs injected through different routes(the hepatic artery or tail vein)into rats with LC was detected by magnetic resonance imaging(MRI),photoacoustic imaging(PAI),and Prussian blue staining.Results:Synthesized Au-Fe3O4 silica NPs consisted of a core(star-shaped Au NPs)and an outside silica layer doped with Fe3O4 NPs.After 24 h coincubation with 2.0 OD concentration of NPs,the viability of BM-MSCs was 77.91%±5.86%and the uptake of Au and Fe were(22.65±1.82)µg/mL and(234.03±11.47)µg/mL,respectively.The surface markers of labeled BM-MSCs unchanged significantly.Labeled BMMSCs have osteogenic and adipogenic differentiation potential.Post injection in vivo,rat livers were hypointense on MRI and hyperintense on PAI.Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group.The severity of LC of the rats in the hepatic artery group was significantly alleviated.Conclusions:Au-Fe3O4 silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BMMSCs was the optimal route for the treatment of LC.展开更多
Because of the intrinsic defects of traditional treatment of cancer,it is quite needed to construct novel theranostic nanoagents that can not only improve the accuracy of imaging diagnosis but also achieve highly effi...Because of the intrinsic defects of traditional treatment of cancer,it is quite needed to construct novel theranostic nanoagents that can not only improve the accuracy of imaging diagnosis but also achieve highly efficient therapy of cancer.Herein,we fabricated polydopamine-functionalized ammonium holmium fluoride nanocomposites(AHF@PDA)for dual-modality bioimaging(magnetic resonance imaging(MRI)and computed tomography(CT))owing to the high X-ray attenuation feature and magnetic property of Ho^(3+).Moreover,PDA shell endows AHF@PDA with excellent photothermal conversion performances and robust biocompatibility,leading to good treatment effect in vitro and in vivo.All above positive results certify that AHF@PDA have good potential as theranostic agents for clinical application in the future.展开更多
Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low effica...Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones.Here,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD.By simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T cells.The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis.Together,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance.展开更多
A biodegradable tumor targeting nano-probe based on poly(ε-caprolactone)-b-poly(ethylene glycol) block copolymer (PCL-b-PEG)micelle functionalized with a magnetic resonance imaging (MRI) contrast agent diethy...A biodegradable tumor targeting nano-probe based on poly(ε-caprolactone)-b-poly(ethylene glycol) block copolymer (PCL-b-PEG)micelle functionalized with a magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd+) on the shell and a near-infrared (NIR) dye in the core for magnetic resonance and optical dual-modality imaging was prepared. The longitudinal relaxivity (rl) of the PCL-b-PEG- DTPA-Gd3+ micelle was 13.4 (mmol/L)^-1s^-1, three folds of that of DTPA-Gd3+, and higher than that of many polymeric contrast agents with similar structures. The in vivo optical imaging of a nude mouse bearing xenografied breast tumor showed that the dual-modality micelle preferentially accumulated in the tumor via the folic acid-mediated active targeting and the passive accumulation by the enhanced permeability and retention (EPR) effect. The results indicated that the dualmodality micelle is a promising nano-probe for cancer detection and diagnosis.展开更多
We propose a high-speed all-optic dual-modal system that integrates spectral domain optical coherence tomography and photoacoustic microscopy(PAM).A 3*3 coupler-based interfer-ometer is used to remotely detect the sur...We propose a high-speed all-optic dual-modal system that integrates spectral domain optical coherence tomography and photoacoustic microscopy(PAM).A 3*3 coupler-based interfer-ometer is used to remotely detect the surface vibration caused by photoacoustic(PA)waves.Three outputs of the interferometer are acquired simultaneously with a multi-channel data ac-quisition card.One channel data with the highest PA signal detection sensitivity is selected for sensitivity compensation.Experiment on the phantom demonstrates that the proposed method can sucessfully compensate for the loss of intensity caused by sensitivity variation.The imaging speed of the PAM is improved compared to our previous system.The total time to image a sample with 256×256 pixels is~20s.Using the proposed system,the microvasculature in the mouse auricle is visualized and the blood flow state is accessed.展开更多
A universal platform with M_n doping and hyaluronic acid (HA) modification, based on mesoporous silica (mSiO2), was designed and used as a basic multifunctional material with magnetic resonance (MR) imaging. Fur...A universal platform with M_n doping and hyaluronic acid (HA) modification, based on mesoporous silica (mSiO2), was designed and used as a basic multifunctional material with magnetic resonance (MR) imaging. Furthermore, we added flexible functions through the addition of functional molecules. Specially, two typical compounds, hydrophobic perfluorooctyl bromide (PFOB) and hydrophilic doxorubicin (DOX), were loaded into the channels to obtain PFOB@Mn@mSiO2@HA (PMMH) or DOX@Mn@mSiO2@HA (DMMH) or imaging and therapy, respectively. The were highly targeted to the lymph system in nanoparticles for dual-mode imaging PMMH and DMMH nanoparticles vitro and in vivo. MR and ultrasound imaging of PMMH nanoparticles were performed in the lymph system, while MR imaging and chemotherapy of DMMH nanoparticles was used to detect cancer. These results showed that both PMMH and DMMH nanoparficles can be designed with high lymph targeting efficiency. PMMH nanoparticles are a dual-mode contrast agent for both ultrasound and MR imaging for the lymph system and DMMH nanoparticles are powerful agents for the combined diagnosis and therapy of cancer in vivo.展开更多
Theranostic nanodrugs combining magnetic resonance imaging(MRI)and cancer therapy have attracted extensive interest in cancer diagnosis and treatment.Herein,a manganese(Mn)-doped mesoporous polydopamine(Mn-MPDA)nanodr...Theranostic nanodrugs combining magnetic resonance imaging(MRI)and cancer therapy have attracted extensive interest in cancer diagnosis and treatment.Herein,a manganese(Mn)-doped mesoporous polydopamine(Mn-MPDA)nanodrug incorporating the nitric oxide(NO)prodrug BNN6 and immune agonist R848 was developed.The nanodrug responded to the H^(+)and glutathione being enriched in tumor microenvironment to release R848 and Mn^(2+).The abundant Mn^(2+)produced through a Fenton-like reaction enabled a highly sensitive T1-T2 dual-mode MRI for monitoring the tumor accumulation process of the nanodrug,based on which an MRI-guided laser irradiation was achieved to trigger the NO gas therapy.Meanwhile,R848 induced the re-polarization of tumor-promoting M2-like macrophage to a tumoricidal M1 phenotype.Consequently,a potent synergistic antitumor effect was realized in mice bearing subcutaneous 4T1 breast cancer,which manifested the great promise of this multifunctional nanoplatform in cancer treatment.展开更多
Mesenchymal stem cells(MSCs)hold great promise in regenerative medicine and received overwhelm-ing concerns to promote their therapeutic effects.Owing to the shortage of MSCs-specific biomarkers,bimodal imaging nanopr...Mesenchymal stem cells(MSCs)hold great promise in regenerative medicine and received overwhelm-ing concerns to promote their therapeutic effects.Owing to the shortage of MSCs-specific biomarkers,bimodal imaging nanoprobes with integrated complementary information are of great importance in ameliorating the efficacy of MSCs terminal tracking.In this study,a noninvasive dual-mode imaging nanoprobe with enhanced detection sensitivity and spatial resolution based on alloyed Gd:AgInS_(2)/ZnS quantum dots(QDs)was first fabricated through a microwave-assisted heating method.The QDs with red emissive fluorescence exhibit excellent biocompatibility in MSCs under a confocal microscope.As for magnetic resonance imaging(MRI),the longitudinal relaxation rate of 11.1420 mM^(-1) S^(-1) of Gd:AgInS_(2)/ZnS QDs was achieved,which was 1.7 times higher than that of commercial MRI contrast agent(6.4667 mM^(-1) S^(-1)).Furthermore,the cellular internalization of Gd:AgInS_(2)/ZnS QDs exerts no significant effect on the adipogenesis of MSCs and is conducive to the observation of further adipogenic differentiation.Our work helps to verify the promising prospect to develop a bimodal nanoprobe of fluorescence/MRI based on Gd:AgInS_(2)/ZnS QDs,which could monitor the differentiation and migration of MSCs for further therapeu-tic approach.展开更多
The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same t...The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time,making MRI a more flexible imaging modality for complicated applications.In this work,three Gadolinium-diethylene-triaminepentaaceticacid(Gd-DTPA)complex conjugated superparamagnetic iron oxide(SPIO)nanoparticles with different Gd/Fe molar ratio(0.94,1.28 and 1.67)were prepared as T_(1)-T_(2) dual-mode MRI probes,named as SPIO@PEG-GdDTPA0.94,SPIO@PEGGdDTPA1.28 and SPIO@PEG-GdDTPA1.67,respectively.All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3þchelate stability.SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67.SPIO@PEG-GdDTPA0.94 nanocomposites with r1(8.4mM^(-1)s^(-1)),r2(83.2mM^(-1)s^(-1))and relatively ideal r2/r1 ratio(9.9)were selected for T_(1)-T_(2) dual-mode MRI of blood vessels and liver tissue in vivo.Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner.Importantly,one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h.Overall,the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians,e.g.saving time,lowering side effects and collecting data of different organs sequentially.展开更多
Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluores...Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluorescence chromophores,an aggregation-induced emission molecule tetraphenylethylene(TPE)-conjugated amphiphilic polyethylenimine(PEI)covered superparamagnetic iron oxide(Alkyl-PEI-LAC-TPE/SPIO nanocomposites)was prepared as an MR/optical dual-mode probe.Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity(352 Fe mM1s1)than a commercial contrast agent Feridex(120 Fe mM1s1)at 1.5 T.The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE.Reducing alkane chain grafting ratio aggravated the stack of TPE,increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites.Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity.As an MR/optical imaging probe,Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.展开更多
基金The authors would like to thank X.Zhang,faculty of XinAoMDT Technology Co.,Ltd.,for the work of system software development.This work is supported by the National Natural Science Foundation of China under Grant Nos.81071191,60831003,30930092,30872633the Tsinghua-Yue-Yuen Medical Science Foundationthe National Basic Research Program of China(973)under Grant No.2011CB707701.
文摘We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast cancer cells which expressed redfluorescent protein(RFP).For FMT system,reflective illumination mode was adopted with full-angle data acquisition.[18F]-Fluorodeoxyglucose([18F]-FDG)was used as radioactive tracer for PET.Both data were acquired simultaneously and then reconstructed separately before fusion.Fluorescent tomography results showed exactly where the tumor was located while PET results offered more metabolic information.Results confirmed feasibility for tumor detection and showed superiority to single modality imaging.
文摘The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as the core can significantly reduce the signal of Fe3O4@MnO2@PAA nanoparticles.MnO2 nanoshells can be decomposed into paramagnetic Mn2+under the acidic environment in the tumor,which enhanced the T1 signal.The pH-responsive T1/T2 dual-mode magnetic resonance imaging(MRI)contrast agent had good sensitivity and specificity,providing more comprehensive and detailed information for tumor diagnosis.In addition,Fe3O4@MnO2@PAA nanoparticles showed excellent absorption capacity in the near-infrared region(NIR),which could be used as a good photothermal conversion material to mediate photothermal treatment of tumors.Therefore,the pHresponsive dual-mode MRI nanoparticle-mediated photothermal therapy showed good application potential in tumor treatment and diagnosis.
基金the National Natural Science Foundation of China(Grant Nos.21573040 and 21603029)the Natural Science Foundation and Science and Technology Development Planning of Jilin Province(20150204086GX and20170520148JH)+3 种基金the Fundamental Research Funds for the Central Universities(2412016KJ007 and 2412016KJ020)the China Postdoctoral Science Foundation(2016M600224)the Jilin Provincial Research Foundation for Basic Research(20160519012JH)Jilin Provincial Key Laboratory of Advanced Energy Materials(Northeast Normal University)
文摘A facile strategy to fabricate gold nanorod@polyacrylic acid/calcium phosphate(Au NR@-PAA/Ca P) yolk–shell nanoparticles(NPs) composed with a PAA/Ca P shell and an Au NR yolk is reported. The asobtained Au NR@PAA/Ca P yolk–shell NPs possess ultrahigh doxorubicin(DOX) loading capability(1 mg DOX/mg NPs), superior photothermal conversion property(26%)and p H/near-infrared(NIR) dual-responsive drug delivery performance. The released DOX continuously increased due to the damage of the Ca P shell at low p H values. When the DOX-loaded Au NR@PAA/Ca P yolk–shell NPs wereexposed to NIR irradiation, a burst-like drug release occurs owing to the heat produced by the Au NRs. Furthermore,Au NR@PAA/Ca P yolk–shell NPs are successfully employed for synergic dual-mode X-ray computed tomography/photoacoustic imaging and chemo-photothermal cancer therapy. Therefore, this work brings new insights for the synthesis of multifunctional nanomaterials and extends theranostic applications.
基金Supported by Italian Ministry of Instruction and Research,No.DM18604-Bando Laboratori-DD MIUR 14.5.2005 n.602/Ric/2005FESR PO Apulia Region 2007-2013-Action 1.2.4,No.3Q5AX31the Progetto Bandiera NANOMAX ENCODER
文摘AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents(NPCAs) for echographic medical imaging at low ultrasound(US) frequency. METHODS: We synthesized three different nanosized structures:(1) Pure silica nanospheres(SiNSs);(2) FePt-iron oxide(FePt-IO)-coated SiNSs; and(3) IOcoated SiNSs, employing three different diameter of SiNS-core(160, 330 and 660 nm). Tissue mimicking phantoms made of agarose gel solution containing 5 mg of different NPCAs in 2 mL-Eppendorf tubes, were insonified by a commercial echographic system at three different low US pulse values(2.5, 3.5 and 4.5 MHz). The raw radiofrequency signal, backscattered from each considered NPCA containing sample, has been processed in order to calculate the US average backscatter intensity and compare the acoustic behavior of the different NPCA types. RESULTS: The highest US contrast was exhibited by pure SiNSs; FePt-IO-coated SiNSs acoustical behavior followed a similar trend of pure SiNSs with a slight difference in terms of brightness values. The acoustic response of the examined NPCAs resulted function of both SiNS diameter and US frequency. Specifically, higher US frequencies determined higher value of the backscatter for a given SiNS diameter. Frequencydependent enhancement was marked for pure SiNSs and became less remarkable for FePt-IO-coated SiNSs, whereas IO-coated SiNSs resulted almost unaffected by such frequency variations. Pure and FePt-IO-coated SiNSs evidenced an image backscatter increasing with the diameter up to 330 nm. Conversely, among the types of NPCA tested, IO-coated SiNSs showed the lowest acoustical response for each synthesized diameter and employed US frequency, although a diameter-dependent raising trend was evidenced. CONCLUSION: The US characterization of magnetically covered SiNS shows that FePt-IO, rather than IO, was the best magnetic coating for realizing NPCAs suitable for dual mode imaging of deep organs, combining US and magnetic resonance imaging.
基金supported by the Beijing Natural Science Foundation,China(No.7232342)the National Key Research and Development Program of China(No.2021YFC2101500)+1 种基金the Project of Academy of Medical Sciences Newton Advanced Fellowship(No.NAFR131015)the Project of the China Scholarship Council.
文摘The combination of near-infrared(NIR)fluorescence imaging(FLI)and photoacoustic imaging(PAI)can effectively compensate for each other’s inherent limitations,which can provide reliable and rich information on tumor biology.Therefore,the development of FL/PA dual-modality imaging probes is beneficial for achieving precision cancer diagnosis and treatment.Herein,we designed an efficient phototherapy agent methoxy bithiophene indene(OTIC),which was based on aggregation-induced emission(AIE)active fluorophores.To improve the water dispersion and enrichment of OTIC at the tumor site,OTIC nanoparticles(OTIC NPs)were prepared by a nanoprecipitation method.The balance between radiation and non-radiation energy dissipation was regulated by the strong donor-acceptor interaction and intramolecular motion.So OTIC NPs exhibited bright NIR fluorescence,photoacoustic signals,efficient generation of reactive oxygen species,and high photothermal conversion efficiency under NIR irradiation.Accurate imaging of the tumor and mice sentinel lymph nodes(SLNs)with OTIC NPs was visualized by NIR FL/PA dual-modal imaging.With the comprehensive imaging information provided by OTIC NPs in vivo,tumors were ablated under laser irradiation,which greatly improved the therapeutic efficacy.OTIC NPs would be possible to realize the precise guidance of FL/PA imaging for tumor treatment in the future clinical application.
基金supported by the National Natural Science Foundation of China(No.21571168)
文摘Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in serving as pH-responsive T1-T2^*dual-modal magnetic resonance(MR)imaging contrast agents.The released Mn^2+shortened T1 relaxation time,meanwhile the superparamagnetic Fe3O4 enhanced T2 contrast imaging.The release rate of Mn ions reaches 31.66%under the condition of pH=5.0,which is similar to tumor microenvironment and organelles.Cytotoxicity assays show that MnSiO3@Fe3O4@C NPs have minor toxicity,even at high concentrations.After intravenous injection of MnSiO3@Fe3O4@C NPs,a rapid contrast enhancement in tumors was achieved with a significant enhancement of 132%after 24 h of the administration.Moreover,a significant decreasement of 53.8%was witnessed in T2 MR imaging signal.It demonstrated that MnSiO3@Fe3O4@C NPs can act as both positive and negative MR imaging contrast agents.Besides,owing to the pH-responsive degradation of mesoporous MnSiO3,MnSiO3@Fe3O4@C NPs can also be used as potential drug systems for cancer theranostics.
基金the Scientific and Technological Achievements Transformation Fund of West China Hospital,Sichuan University(grant CGZH21002)the Innovative Research Project of Sichuan University(grant 2022SCUH00132)the Sichuan Foundation for Distinguished Young Scholars(grant 2022JDJQ0049).
文摘The prognosis of glioblastoma(GBM)remains challenging,primarily due to the lack of a precise,effective imaging technique for comprehensively characterization.Addressing GBM diagnostic challenges,our study introduces an innovative dual-modal imaging that merges near-infrared(NIR)fluorescent imaging with magnetic resonance imaging(MR).This method employs superparamagnetic iron oxide nanoparticies coated with NIR fluorescent dyes,specifically Cyanine 7,and targeted peptides.This synthetic probe facilitates MRI functionality through superparamagnetic iron oxide nanoparticles,provides NIR imaging capability via Cyanine 7 and enhances tumor targeting trough peptide interactions,offering a comprehensive diagnostic tool for GBM.Notably,the probe traverses the blood-brain barrier,targeting GBM in vivo via peptides,producing clear and discermible images in both modalities.Cytotoxicity and histopathology assessments confirm the probe's favorable safet profile.These findings suggest that the dual-modal MRINIR fluorescent imaging probe could revolutionize GBM prognosis and survival rate which can also be extended to other tumors type.
基金supported by the National Natural Science Foundation of China(22077030,22271092,21977018,82173657)the China Postdoctoral Science Foundation(2021M701196)。
文摘Taking apart in numerous physiological and pathological activities,hydrogen sulfide(H_(2)S)has been selected as an excellent target spot for the early diagnosis of cancer.So far,there are many mature probes that apply single optical imaging to monitor endogenous H_(2)S.Nevertheless,a single modality is not an ideal method to afford accurate diagnostic information in comprehensive biological organisms.Herein,we developed a dual-modal imaging probe BWS.This designed probe showed a specific response to H_(2)S with both chemiluminescence and NIR fluorescence light-up.The concurrence of fluorescence and chemiluminescence signal provided“double insurances”for highly accurate monitoring of H_(2)S.Satisfactorily,this dual-modal imaging probe performed precise visualization of endogenous H_(2)S in living cells and in vivo.We envisaged that this chemiluminescence/fluorescence real-time dual-modality strategy for H_(2)S detection will expand and optimize the multimodal imaging methods for efficient diagnosis and treatment of cancer.
基金supported by the National Natural Science Foundation of China(Nos.82201135,22174070,and 61905122)Nanjing Clinical Research Center for Oral Diseases(No.2019060009)+2 种基金General project of Jiangsu Provincial Health Commission(No.M2021077)Scientific research fund of Jiangsu Medical Association(No.SYH-3201150-0007(2021002))the Natural Science Foundation of Jiangsu Province(No.BK20190735).
文摘Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the oral and maxillofacial region.Due to its unique location,earlier and more accurate diagnosis and more minimally invasive treatment of OSCC is of major importance.Herein,gadolinium-containing semiconductor polymer nanoparticles(SPN-Gd)were designed and prepared.The nanoparticles consist of a near-infrared(NIR)absorption semiconductor polymer(PCPDTBT)served as fluorescence signal source and a photothermal conversion agent(PTA)and a gadolinium-grafted triblock amphiphilic copolymer(F127-DTPA-Gd)served as a magnetic resonance imaging(MRI)contrast agent and nanocarrier.The experiments in vivo showed that SPN-Gd could act as an MRI contrast agent and optical image agent with a long retention time,and it had a significant inhibiting effect on tumors of OSCC mice model through photothermal therapy(PTT).Thus our study provides a simple nanotheranostic platform composed of two components for efficient MR/fluorescence dual-modal imaging-guided PTT.
基金supported by National Natural Science Foundation of China(52073193,51873120,81621003,51903173)1⋅3⋅5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21013)+1 种基金Science and Technology Program of Sichuan province(2020YJ0231)China Postdoctoral Science Foundation(2021M692255).
文摘Nanoprobes that offer both fluorescence imaging(FI)and magnetic resonance imaging(MRI)can provide supplementary information and hold synergistic advantages.However,synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups,high stability,great biocompatibility and desired dual-modality imaging results remains challenging.In this study,we used an amphiphilic block polymer from(ethylene glycol)methyl ether methacrylate(OEGMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)derivatives as a carrier to conjugate a MR contrast agent,Gd-DOTA,and a two-photon fluorophore with an aggregation-induced emission(AIE)effect,TPBP,to construct a MR/two-photon fluorescence dual-modality contrast agent,Gd-DOTA-TPBP.Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r_(1)value for Gd-DOTA-TPBP,revealing a great MR imaging resolution.The contrast agent specifically accumulated in the tumor region,allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging.Meanwhile,coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity,but also significantly enhanced its imaging performance in an aqueous phase.Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI.Since high-resolution,complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP,it has great potential in the early phase of disease diagnosis.
基金funded by grants from The National Natural Science Foundation of China (No.81671800)。
文摘Background and Aims:Stem cell transplantation is a potential treatment option for liver cirrhosis(LC).Accurately and noninvasively monitoring the distribution,migration,and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms.Our study aimed to develop Au-Fe3O4 silica nanoparticles(NPs)as tracking nanoplatforms for dualmodal stem cell imaging.Methods:Au-Fe3O4 silica NPs were synthesized by seed-mediated growth method and co-precipitation.The efficiency and cytotoxicity of the NPslabeled bone marrow-derived mesenchymal stem cells(BMMSCs)were evaluated by Cell Counting Kit-8 assays,ICPMS,phenotypic characterization,and histological staining.The biodistribution of labeled BM-MSCs injected through different routes(the hepatic artery or tail vein)into rats with LC was detected by magnetic resonance imaging(MRI),photoacoustic imaging(PAI),and Prussian blue staining.Results:Synthesized Au-Fe3O4 silica NPs consisted of a core(star-shaped Au NPs)and an outside silica layer doped with Fe3O4 NPs.After 24 h coincubation with 2.0 OD concentration of NPs,the viability of BM-MSCs was 77.91%±5.86%and the uptake of Au and Fe were(22.65±1.82)µg/mL and(234.03±11.47)µg/mL,respectively.The surface markers of labeled BM-MSCs unchanged significantly.Labeled BMMSCs have osteogenic and adipogenic differentiation potential.Post injection in vivo,rat livers were hypointense on MRI and hyperintense on PAI.Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group.The severity of LC of the rats in the hepatic artery group was significantly alleviated.Conclusions:Au-Fe3O4 silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BMMSCs was the optimal route for the treatment of LC.
基金supported by the National Natural Science Foundation of China(51502284,21834007,21521092,21590794,52022094,21673220)the Program of Science and Technology Development Plan of Jilin Province of China(20170101186JC)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB20030300)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2019232)。
文摘Because of the intrinsic defects of traditional treatment of cancer,it is quite needed to construct novel theranostic nanoagents that can not only improve the accuracy of imaging diagnosis but also achieve highly efficient therapy of cancer.Herein,we fabricated polydopamine-functionalized ammonium holmium fluoride nanocomposites(AHF@PDA)for dual-modality bioimaging(magnetic resonance imaging(MRI)and computed tomography(CT))owing to the high X-ray attenuation feature and magnetic property of Ho^(3+).Moreover,PDA shell endows AHF@PDA with excellent photothermal conversion performances and robust biocompatibility,leading to good treatment effect in vitro and in vivo.All above positive results certify that AHF@PDA have good potential as theranostic agents for clinical application in the future.
基金supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01,China)ZJ Lab,Shanghai Natural Science Foundation(Grant No.18ZR1405700,China)+3 种基金National Natural Science Foundation of China(Fund Nos.81773283 and 81901697)Shanghai Sailing Program(Grant No.18YF1403000,China)Shanghai Chest Hospital Project of Collaborative Innovation(Grant No.YJXT20190203,China)the Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure(SKL201908SIC,China)。
文摘Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones.Here,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD.By simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T cells.The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis.Together,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance.
基金supported by the National Natural Science Foundation of China(No.20904046)the National Basic Research Program(973 Program)(No.2009CB526403) of China+1 种基金the Doctoral Fund of Ministry of Education of China(No.20090101120159)the Qianjiang Talent Program of Zhejiang Province,China(No.2010R10050)
文摘A biodegradable tumor targeting nano-probe based on poly(ε-caprolactone)-b-poly(ethylene glycol) block copolymer (PCL-b-PEG)micelle functionalized with a magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd+) on the shell and a near-infrared (NIR) dye in the core for magnetic resonance and optical dual-modality imaging was prepared. The longitudinal relaxivity (rl) of the PCL-b-PEG- DTPA-Gd3+ micelle was 13.4 (mmol/L)^-1s^-1, three folds of that of DTPA-Gd3+, and higher than that of many polymeric contrast agents with similar structures. The in vivo optical imaging of a nude mouse bearing xenografied breast tumor showed that the dual-modality micelle preferentially accumulated in the tumor via the folic acid-mediated active targeting and the passive accumulation by the enhanced permeability and retention (EPR) effect. The results indicated that the dualmodality micelle is a promising nano-probe for cancer detection and diagnosis.
基金This work was supported in part by the National Natural Science Foundation of China(Grant Nos.61771119,61901100 and 62075037)the Natural Science Foundation of Hebei Province(Grant Nos.H2019501010,F2019501132,E2020501029 and F2020501040).
文摘We propose a high-speed all-optic dual-modal system that integrates spectral domain optical coherence tomography and photoacoustic microscopy(PAM).A 3*3 coupler-based interfer-ometer is used to remotely detect the surface vibration caused by photoacoustic(PA)waves.Three outputs of the interferometer are acquired simultaneously with a multi-channel data ac-quisition card.One channel data with the highest PA signal detection sensitivity is selected for sensitivity compensation.Experiment on the phantom demonstrates that the proposed method can sucessfully compensate for the loss of intensity caused by sensitivity variation.The imaging speed of the PAM is improved compared to our previous system.The total time to image a sample with 256×256 pixels is~20s.Using the proposed system,the microvasculature in the mouse auricle is visualized and the blood flow state is accessed.
基金The work is supported by Shanghai Rising-Star Program (No. 13QB1402200), Shanghai Minhang district talent development special fund, National Key Technology Research and Development Program (No. 2014BAK05B02) and National Natural Science Foundation of China (Nos. 81271638 and 81371622).
文摘A universal platform with M_n doping and hyaluronic acid (HA) modification, based on mesoporous silica (mSiO2), was designed and used as a basic multifunctional material with magnetic resonance (MR) imaging. Furthermore, we added flexible functions through the addition of functional molecules. Specially, two typical compounds, hydrophobic perfluorooctyl bromide (PFOB) and hydrophilic doxorubicin (DOX), were loaded into the channels to obtain PFOB@Mn@mSiO2@HA (PMMH) or DOX@Mn@mSiO2@HA (DMMH) or imaging and therapy, respectively. The were highly targeted to the lymph system in nanoparticles for dual-mode imaging PMMH and DMMH nanoparticles vitro and in vivo. MR and ultrasound imaging of PMMH nanoparticles were performed in the lymph system, while MR imaging and chemotherapy of DMMH nanoparticles was used to detect cancer. These results showed that both PMMH and DMMH nanoparficles can be designed with high lymph targeting efficiency. PMMH nanoparticles are a dual-mode contrast agent for both ultrasound and MR imaging for the lymph system and DMMH nanoparticles are powerful agents for the combined diagnosis and therapy of cancer in vivo.
基金supported by the National Natural Science Foundation of China(Nos.51933011 and 31971296)the Key Areas Research and Development Program of Guangzhou(No.202007020006)+3 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020A1515010523)Guangzhou Science and Technology Bureau(No.202102010181)Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument(Sun Yat-sen University,No.2020B1212060077)approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University(SYSU-IACUC-2021-000225).
文摘Theranostic nanodrugs combining magnetic resonance imaging(MRI)and cancer therapy have attracted extensive interest in cancer diagnosis and treatment.Herein,a manganese(Mn)-doped mesoporous polydopamine(Mn-MPDA)nanodrug incorporating the nitric oxide(NO)prodrug BNN6 and immune agonist R848 was developed.The nanodrug responded to the H^(+)and glutathione being enriched in tumor microenvironment to release R848 and Mn^(2+).The abundant Mn^(2+)produced through a Fenton-like reaction enabled a highly sensitive T1-T2 dual-mode MRI for monitoring the tumor accumulation process of the nanodrug,based on which an MRI-guided laser irradiation was achieved to trigger the NO gas therapy.Meanwhile,R848 induced the re-polarization of tumor-promoting M2-like macrophage to a tumoricidal M1 phenotype.Consequently,a potent synergistic antitumor effect was realized in mice bearing subcutaneous 4T1 breast cancer,which manifested the great promise of this multifunctional nanoplatform in cancer treatment.
基金financially supported by the National Natural Science Foundation of China(NSFC,No.62074044)the Zhongshan-Fudan Joint Innovation Center,and the Jihua Laboratory Projects of Guangdong Province(No.X190111UZ190).
文摘Mesenchymal stem cells(MSCs)hold great promise in regenerative medicine and received overwhelm-ing concerns to promote their therapeutic effects.Owing to the shortage of MSCs-specific biomarkers,bimodal imaging nanoprobes with integrated complementary information are of great importance in ameliorating the efficacy of MSCs terminal tracking.In this study,a noninvasive dual-mode imaging nanoprobe with enhanced detection sensitivity and spatial resolution based on alloyed Gd:AgInS_(2)/ZnS quantum dots(QDs)was first fabricated through a microwave-assisted heating method.The QDs with red emissive fluorescence exhibit excellent biocompatibility in MSCs under a confocal microscope.As for magnetic resonance imaging(MRI),the longitudinal relaxation rate of 11.1420 mM^(-1) S^(-1) of Gd:AgInS_(2)/ZnS QDs was achieved,which was 1.7 times higher than that of commercial MRI contrast agent(6.4667 mM^(-1) S^(-1)).Furthermore,the cellular internalization of Gd:AgInS_(2)/ZnS QDs exerts no significant effect on the adipogenesis of MSCs and is conducive to the observation of further adipogenic differentiation.Our work helps to verify the promising prospect to develop a bimodal nanoprobe of fluorescence/MRI based on Gd:AgInS_(2)/ZnS QDs,which could monitor the differentiation and migration of MSCs for further therapeu-tic approach.
基金supported by National Natural Science Foundation of China(NSFC,No.51903174 and 52073192)Innovative Research Groups of the National Natural Science Foundation of China(81621003).
文摘The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time,making MRI a more flexible imaging modality for complicated applications.In this work,three Gadolinium-diethylene-triaminepentaaceticacid(Gd-DTPA)complex conjugated superparamagnetic iron oxide(SPIO)nanoparticles with different Gd/Fe molar ratio(0.94,1.28 and 1.67)were prepared as T_(1)-T_(2) dual-mode MRI probes,named as SPIO@PEG-GdDTPA0.94,SPIO@PEGGdDTPA1.28 and SPIO@PEG-GdDTPA1.67,respectively.All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3þchelate stability.SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67.SPIO@PEG-GdDTPA0.94 nanocomposites with r1(8.4mM^(-1)s^(-1)),r2(83.2mM^(-1)s^(-1))and relatively ideal r2/r1 ratio(9.9)were selected for T_(1)-T_(2) dual-mode MRI of blood vessels and liver tissue in vivo.Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner.Importantly,one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h.Overall,the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians,e.g.saving time,lowering side effects and collecting data of different organs sequentially.
基金This work was financially supported by the National Natural Science Foundation of China(NSFC,No.51903174 and 52073192)Innovative Research Groups of the National Natural Science Foundation of China(81621003)+1 种基金Chengdu Science and Technology Program(2019-YF05-00318-SN)the Fundamental Research Funds for Central Universities(2021SCU12070).
文摘Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluorescence chromophores,an aggregation-induced emission molecule tetraphenylethylene(TPE)-conjugated amphiphilic polyethylenimine(PEI)covered superparamagnetic iron oxide(Alkyl-PEI-LAC-TPE/SPIO nanocomposites)was prepared as an MR/optical dual-mode probe.Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity(352 Fe mM1s1)than a commercial contrast agent Feridex(120 Fe mM1s1)at 1.5 T.The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE.Reducing alkane chain grafting ratio aggravated the stack of TPE,increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites.Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity.As an MR/optical imaging probe,Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.