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1.
RSC Adv ; 14(11): 7609-7615, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38444979

ABSTRACT

In this study, the effect of the green liquor (GL)-sulfite pretreatment on bamboo for enzymatic hydrolysis was investigated. The performance characterization of the pretreated bamboo substrates, including the chemical composition, and the structural characteristics was carried out. The results showed that 91.3% of lignin removal was achieved when the sample was treated with a GL loading of 12.0 mL per g-DS at 120 °C for 1 h. After 120 h hydrolysis with 18 FPU per g-cellulose for cellulase and 27 CBU per g-cellulose for glucosidase, the glucose yield increased from 54.6% to 89.6%. The SE-treated bamboo could bind more easily to cellulase than GL-sulfite treated bamboo could. The structural changes on the surface of the samples were characterized by SEM. The results indicated that the surface lignin could be effectively removed during pretreatment, thereby decreasing the enzyme-lignin binding activity.

2.
Int J Nanomedicine ; 19: 189-208, 2024.
Article in English | MEDLINE | ID: mdl-38223882

ABSTRACT

Purpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC. Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety. Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells. Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy.


Subject(s)
Carcinoma, Hepatocellular , Hyperthermia, Induced , Liver Neoplasms , Nanoparticles , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Phototherapy/methods , Doxorubicin , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Hyperthermia, Induced/methods , Cell Line, Tumor
3.
Food Chem ; 439: 138170, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38118227

ABSTRACT

The carryover of trace allergens in complex food matrices poses challenges for detection techniques. Here, we demonstrate an accurate UPLC-MS/MS quantification assay for the shrimp allergen tropomyosin with a full-length isotope-labelled recombinant tropomyosin (TM-I) internal standard in complex food matrices. The TM-I, expressed based on the SILAC technique, exhibited a high isotope labelling ratio (>99%), purity, and alignment with the natural sequence. This method determined the tropomyosin ranging from 0.2 to 100 ng/mL. Mean recoveries ranged from 89 to 116%, with intra- and inter-day RSDs below 12%, for three signature peptides across three types of commercially processed food matrices. The limits of quantitation were 1 µg/g in pop food and sauce, and 10 µg/g in surimi product, respectively. This study supports the use of recombinant full-length isotope-labelled proteins rather than stable-isotope labelling peptides as internal standards to achieve more accurate quantitation of food allergens as the digestion error is corrected.


Subject(s)
Food Hypersensitivity , Tandem Mass Spectrometry , Animals , Tandem Mass Spectrometry/methods , Chromatography, Liquid , Tropomyosin , Liquid Chromatography-Mass Spectrometry , Allergens , Crustacea , Peptides , Recombinant Proteins , Isotopes
4.
Food Chem ; 425: 136467, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37270884

ABSTRACT

Nontargeted analysis for chemical hazards is highly desirable in controlling food safety to ensure human health. As the dominating interference in fat-rich foodstuffs, lipids removal is a great challenge in sample pretreatment. Herein, diverse lipids from both animal and vegetable oils are effectively removed and 565 chemical hazards with various physicochemical properties are used for method validation. These benefits are from the designed magnetic amino-rich hyper-crosslinked core-shell polymeric composites (Fe3O4@poly(MAAM-co-EGDMA)) and the application of an auto extraction system. Among them, the amino groups are the key factors for lipid removal. Theoretical calculations, isothermal titration calorimetry (ITC), and functional monomer replacement demonstrated that the mechanisms to universally capture free fatty acids (FFAs) and triglycerides (TGs) are electrostatic interaction and supplemented by hydrogen bonding. Overall, this work highlights the great application potentials of polymeric adsorbents as sample pretreatment materials for nontargeted analysis in food safety.


Subject(s)
Plant Oils , Polymers , Animals , Humans , Polymers/chemistry , Food Safety , Physical Phenomena , Magnetic Phenomena
5.
Food Chem ; 415: 135766, 2023 Jul 30.
Article in English | MEDLINE | ID: mdl-36868064

ABSTRACT

Carbendazim, a systemic fungicide, is one of the most commonly detected pesticides in cowpeas. Pickled cowpea is a fermented vegetable product with unique flavor favored in China. The dissipation and degradation of carbendazim were investigated in the pickled process. The degradation rate constant of carbendazim in pickled cowpeas was 0.9945 and the half-life of the carbendazim was 14.06 ± 0.82 d. Seven transformation products (TPs) were identified in the pickled process. Furthermore, the toxicity of some TPs show more harmful to three aquatic organisms (TP134) and rats (all the identified TPs) than carbendazim. And most of the TPs posed more development toxicity and mutagenicity than carbendazim. 4 out of 7 TPs were discovered in the real pickled cowpea samples. These results shed light on the degradation and biotransformation of the carbendazim in the pickled process, to better understand the potential health risk of pickled food and evaluate the environmental pollution.


Subject(s)
Pesticides , Vigna , Rats , Animals , Carbamates , Biotransformation
6.
J Nanobiotechnology ; 21(1): 112, 2023 Mar 28.
Article in English | MEDLINE | ID: mdl-36978072

ABSTRACT

Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer.


Subject(s)
Breast Neoplasms , Surgery, Computer-Assisted , Female , Humans , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Fibronectins , Fluorescent Dyes/metabolism , Metalloproteases , Optical Imaging/methods , Surgery, Computer-Assisted/methods
7.
Biochim Biophys Acta Rev Cancer ; 1877(5): 188788, 2022 09.
Article in English | MEDLINE | ID: mdl-36049581

ABSTRACT

Histone Deacetylases (HDACs) are abnormally high expressed in various cancers and play a crucial role in regulating gene expression. While HDAC-targeted inhibitors have been rapidly developed and approved in the last twenty years, noninvasive monitoring and visualizing the expression levels of HDACs in tumor tissues might help to early diagnosis in cancer and predict the response to HDAC-targeted cancer therapy. In this review, we summarize the recent advancements in the development of HDAC-targeted probes and their applications in cancer imaging and image-guided surgery. We also discuss the design strategies, advantages and disadvantages of these probes. We hope that this review will provide guidance for the design of HDAC-targeted imaging probes and clinical applications in future.


Subject(s)
Histone Deacetylases , Neoplasms , Histone Deacetylase Inhibitors/metabolism , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Histone Deacetylases/therapeutic use , Humans , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/genetics
8.
Anal Chem ; 94(40): 14012-14020, 2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36166661

ABSTRACT

Breast cancer is the most common malignancy in women and may become worse when a high concentration of hydrazine is absorbed from the environment or drug metabolite. Therefore, rapid and sensitive detection of hydrazine in vivo is beneficial for people's health. In this work, a novel estrogen receptor α (ERα)-targeted near-infrared fluorescence probe was designed to detect hydrazine levels. The probe showed good ERα affinity and an excellent fluorescence response toward hydrazine. Selectivity experiments demonstrated that the probe had a strong anti-interference ability. Mechanistic studies, including mass spectrometry (MS) and density functional theory (DFT) calculation, indicated that intermolecular charge transfer (ICT) progress was hindered when the probe reacted with hydrazine, resulting in fluorescent quenching. In addition, the probe could selectively bind to MCF-7 breast cancer cells with excellent biocompatibility. The in vivo and ex vivo imaging studies demonstrated that the probe could rapidly visualize hydrazine with high contrast in MCF-7 xenograft tumors. Therefore, this probe can serve as a potential tool to robustly monitor hydrazine levels in vivo.


Subject(s)
Breast Neoplasms , Estrogen Receptor alpha , Breast Neoplasms/diagnostic imaging , Female , Fluorescent Dyes/chemistry , Humans , Hydrazines/chemistry , Spectrometry, Fluorescence
9.
Nanotechnology ; 33(45)2022 Aug 23.
Article in English | MEDLINE | ID: mdl-35914421

ABSTRACT

To fabricate a novel stimuli-responsive system enabling controlled drug release and synergistic therapy, yolk-shell shaped bismuth sulfide modified with Au nanoparticles (Au-Bi2S3) was prepared. The Au-Bi2S3nanomaterial with heterojunction structure exhibited excellent photothermal conversion efficiency and considerable free radicals yield under laser irradiation. The drug delivery capacity was confirmed by co-loading Berberine hydrochloride (BBR) and a phase change material 1-tetradecanol (PCM), which could be responsible for NIR light induced thermal controlled drug release.In vitroinvestigation demonstrated that Au-Bi2S3has cell selectivity, and with the assistance of the properties of Au-Bi2S3, the loaded drug could give full play to their cancer cell inhibition ability. Our work highlights the great potential of this nanoplatform which could deliver and control Berberine hydrochloride release as well as realize the synergistic anti-tumor strategy of photothermal therapy, photodynamic therapy and chemotherapy for tumor therapy.


Subject(s)
Berberine , Metal Nanoparticles , Nanoparticles , Neoplasms , Berberine/pharmacology , Berberine/therapeutic use , Bismuth , Cell Line, Tumor , Doxorubicin/pharmacology , Drug Delivery Systems , Drug Liberation , Gold/chemistry , Humans , Nanoparticles/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Pharmaceutical Preparations , Phototherapy , Sulfides
10.
Bioconjug Chem ; 32(1): 161-171, 2021 01 20.
Article in English | MEDLINE | ID: mdl-33337872

ABSTRACT

Early identification and treatment of breast cancer is very important for breast conserving therapy and to improve the prognosis and survival rates of patients. Multifunctional nanotheranostic agents are of particular importance in the field of precise nanomedicine, since they can augment the visualization and treatment of cancer. We developed a novel Bi2S3 nanoparticle coated with a hyaluronic acid (HA)-modified tantalum oxide (TaOx) nanoshell (Bi2S3@TaOx-HA). The as-prepared core/shell nanoparticles exhibited a high Bi2S3 nanoparticle loading efficiency of (67 wt %). The TaOx nanoshell exhibited excellent biocompatibility and computed tomography imaging capacity, and the Bi2S3 nanoparticles exhibited an excellent photothermal transducing performance and computed tomography (CT) and photoacoustic imaging capacity. As a result of these merits, the Bi2S3@TaOx core-shell nanoparticles can act as a theranostic agent for CT/photoacoustically monitored enhanced photothermal therapy. These findings will evoke new interest in future cancer therapeutic strategies based on biocompatible functional nanomaterials.


Subject(s)
Bismuth/chemistry , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Oxides/chemistry , Precision Medicine , Sulfides/chemistry , Tantalum/chemistry , Animals , Biocompatible Materials , Cell Line, Tumor , Female , Humans , Photoacoustic Techniques , Phototherapy/methods , Tomography, X-Ray Computed
11.
ACS Nano ; 14(10): 12679-12696, 2020 10 27.
Article in English | MEDLINE | ID: mdl-32909732

ABSTRACT

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prone to recurrence and metastasis and has no effective treatment. Unsurprisingly, its prognosis is quite poor; early detection methods and effective low-toxicity treatments are urgently needed. To achieve these goals, we designed a multifunctional, U.S. Food and Drug Administration-approved Prussian blue (PB) nanoparticle (NP) with a porous metal organic frame loaded with sorafenib (SF), conjugated with HCC-specific targeting peptide SP94 and the near-infrared dye cyanine (Cy)5.5. These NPs are amenable to multimodal imaging for dynamic monitoring of their biodistribution and tumor-targeting effects. The SP94-PB-SF-Cy5.5 NPs achieved targeted delivery and controlled SF release and exhibited good photothermal effects. In this strategy, photothermal therapy and SF treatment complement each other, reducing the side effects of SF and achieving a therapeutic effect without local tumor recurrence. In addition, the catalase-like ability of the NPs alleviates tumor hypoxia, and their photothermal effects induce immunogenic cell death, leading to the release of tumor-associated antigens. These effects combine to trigger an antitumor immune response; the NPs also displayed promising inhibitory effects on tumor metastasis and recurrence and produced an abscopal effect and long-term immunological memory when combined with antiprogrammed death-ligand 1 (PD-L1) immunotherapy. These safe, multifunctional NPs represent a valuable treatment option for HCC. In addition, this next-generation treatment model may provide some ideas for the management of HCC and other cancers.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Humans , Hypoxia , Immunotherapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Phototherapy , Tissue Distribution
12.
IEEE Trans Med Imaging ; 38(12): 2726-2734, 2019 12.
Article in English | MEDLINE | ID: mdl-31021763

ABSTRACT

Fluorescence molecular tomography (FMT), as a powerful imaging technique in preclinical research, can offer the three-dimensional distribution of biomarkers by detecting the fluorescently labelled probe noninvasively. However, because of the light scattering effect and the ill-pose of inverse problem, it is challenging to develop an efficient reconstruction method, which can provide accurate location and morphology of the fluorescence distribution. In this research, we proposed a novel adaptive Gaussian weighted Laplace prior (AGWLP) regularization method, which assumed the variance of fluorescence intensity between any two voxels had a non-linear correlation with their Gaussian distance. It utilized an adaptive Gaussian kernel parameter strategy to achieve accurate morphological reconstructions in FMT. To evaluate the performance of the AGWLP method, we conducted numerical simulation and in vivo experiments. The results were compared with fast iterative shrinkage (FIS) thresholding method, split Bregman-resolved TV (SBRTV) regularization method, and Gaussian weighted Laplace prior (GWLP) regularization method. We validated in vivo imaging results against planar fluorescence images of frozen sections. The results demonstrated that the AGWLP method achieved superior performance in both location and shape recovery of fluorescence distribution. This enabled FMT more suitable and practical for in vivo visualization of biomarkers.


Subject(s)
Imaging, Three-Dimensional/methods , Tomography, Optical/methods , Algorithms , Animals , Brain/diagnostic imaging , Male , Mice , Mice, Inbred BALB C , Normal Distribution , Phantoms, Imaging
13.
Acta Biomater ; 87: 223-234, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30669004

ABSTRACT

Neuroblastoma accounts for 8-10% of malignancies in infants and children. It is urgent to develop an appropriate theranostic agent for effective diagnosis and therapy of neuroblastoma. Herein, we constructed RVG peptide and IRDye800-conjugated bovine serum albumin-coated triangular gadolinium oxide nanoplates (RVG&IRDye800-Gd2O3 TNs) as a targeting MRI agent for the diagnosis of neuroblastoma preoperation and a fluorescence imaging agent for the guidance of the precise excision of the neuroblastoma in surgery. RVG&IRDye800-Gd2O3 TNs have uniform edge length. The RVG&IRDye800-Gd2O3 TNs show remarkably enhanced affinity to both mouse- and human-derived neuroblastoma cells compared with IRDye800-Gd2O3 TNs (3.07-fold and 3.02-fold, respectively). Because of the increased accumulation in tumor cells, RVG&IRDye800-Gd2O3 TNs exhibit signals threefold to fivefold higher than the surrounding normal tissues, which is propitious to the diagnosis of neuroblastoma preoperation and provides real-time visual guidance of the precise excision of the neuroblastoma. Most importantly, with the guidance of the fluorescence imaging agent, the survival rate increased from 0% to 80% 42 days after surgery compared with that in conventional surgery. These findings indicated that the RVG peptide combined with IRDye800-Gd2O3 TNs has the potential to improve the diagnosis and treatment of patients with neuroblastoma. STATEMENT OF SIGNIFICANCE: In this study, we prepared RVG peptide and IRDye800-conjugated bovine serum albumin-coated triangular gadolinium oxide nanoplates (RVG&IRDye800-Gd2O3 TNs) as a targeting MRI agent for the diagnosis of neuroblastoma preoperation and a fluorescence imaging agent for the guidance of the precise excision of the neuroblastoma during surgery. Neuroblastoma was accurately located by MRI imaging, and the tumor margin could be real-time monitored through near-infrared fluorescence imaging. The RVG&IRDye800-Gd2O3 TNs exhibit signals threefold to fivefold higher than those in the surrounding normal tissues, which is propitious to the diagnosis of the neuroblastoma preoperation and provides real-time visual guidance of the precise excision of the neuroblastoma. With the guidance of the fluorescence imaging agent in surgery, the survival rate increased from 0% to 80% 42 days after surgery compared with that in conventional surgery.


Subject(s)
Contrast Media , Drug Delivery Systems , Gadolinium , Neoplasms, Experimental , Neuroblastoma , Animals , Cell Line, Tumor , Contrast Media/chemistry , Contrast Media/pharmacology , Gadolinium/chemistry , Gadolinium/pharmacology , Humans , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Neoplasms, Experimental/surgery , Neuroblastoma/metabolism , Neuroblastoma/pathology , Neuroblastoma/surgery
14.
Biomaterials ; 183: 173-184, 2018 11.
Article in English | MEDLINE | ID: mdl-30172243

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies with poor patient outcomes often resulting from delayed diagnosis. Therefore, early diagnosis can lead to a better prognosis and improved outcomes. In this study, we have developed a novel conjugate complex of plectin/integrin-targeted bispecific molecular probe, termed Gd-Cy7-PTP/RGD, to be used for magnetic resonance/near-infrared imaging (MRI/NIRF) of pancreatic cancer in vivo. This bispecific molecular probe comprises four parts: Gd(III) for MRI, cyanine 7 (Cy7) for NIRF, the peptide PTP for binding to plectin-1 specifically overexpressed on the surface of PDAC cells, and the peptide RGD for targeting integrin widely expressed on pancreatic duct epithelial cells and angiogenesis. Remarkably, the combination of PTP and RGD greatly increased the targeting efficiency in vitro and in vivo compared to that of either single peptide. Moreover, such bispecific molecular probes target pancreatic neoplasms and angiogenesis simultaneously, producing a "multi-level" targeting effect confirmed by immunofluorescence testing in vitro and in vivo. Under the guidance of MRI/NIRF dual-modality imaging, NIRF-guided delineation of surgical margins during operations was successfully achieved in orthotopic pancreatic cancer. This study promotes further exploration of bispecific molecular probes for clinical application.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnostic imaging , Integrins/metabolism , Magnetic Resonance Imaging/methods , Molecular Probes/chemistry , Optical Imaging/methods , Pancreatic Neoplasms/diagnostic imaging , Plectin/metabolism , Animals , Benzothiazoles/chemistry , Carbocyanines/chemistry , Carcinoma, Pancreatic Ductal/surgery , Cell Line, Tumor , Cell Survival , Coordination Complexes/chemistry , Female , Fluorescent Dyes/chemistry , Gadolinium/chemistry , Humans , Infrared Rays , Margins of Excision , Mice, Inbred BALB C , Mice, Nude , Oligopeptides/chemistry , Pancreatic Neoplasms/surgery
15.
Contrast Media Mol Imaging ; 2018: 9321862, 2018.
Article in English | MEDLINE | ID: mdl-29853812

ABSTRACT

Tumor cell complete extinction is a crucial measure to evaluate antitumor efficacy. The difficulties in defining tumor margins and finding satellite metastases are the reason for tumor recurrence. A synergistic method based on multimodality molecular imaging needs to be developed so as to achieve the complete extinction of the tumor cells. In this study, graphene oxide conjugated with gold nanostars and chelated with Gd through 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid (DOTA) (GO-AuNS-DOTA-Gd) were prepared to target HCC-LM3-fLuc cells and used for therapy. For subcutaneous tumor, multimodality molecular imaging including photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) and the related processing techniques were used to monitor the pharmacokinetics process of GO-AuNS-DOTA-Gd in order to determine the optimal time for treatment. For orthotopic tumor, MRI was used to delineate the tumor location and margin in vivo before treatment. Then handheld photoacoustic imaging system was used to determine the tumor location during the surgery and guided the photothermal therapy. The experiment result based on orthotopic tumor demonstrated that this synergistic method could effectively reduce tumor residual and satellite metastases by 85.71% compared with the routine photothermal method without handheld PAI guidance. These results indicate that this multimodality molecular imaging-guided photothermal therapy method is promising with a good prospect in clinical application.


Subject(s)
Carcinoma, Hepatocellular , Chelating Agents , Gadolinium , Gold , Graphite , Hyperthermia, Induced , Liver Neoplasms, Experimental , Magnetic Resonance Imaging , Metal Nanoparticles , Phototherapy , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Chelating Agents/chemistry , Chelating Agents/pharmacology , Gadolinium/chemistry , Gadolinium/pharmacology , Gold/chemistry , Gold/pharmacology , Graphite/chemistry , Graphite/pharmacology , Humans , Liver Neoplasms, Experimental/diagnostic imaging , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/therapy , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Mice , Mice, Inbred BALB C
16.
Nanoscale ; 10(20): 9594-9601, 2018 May 24.
Article in English | MEDLINE | ID: mdl-29745953

ABSTRACT

Early identification and treatment of hepatocellular carcinoma is very important for improving the prognosis and survival rate of the patient. To enhance the visualization and treatment efficiency of HCC, a theranostic agent has been developed that combines photoacoustic/fluorescence imaging with photothermal therapy for cancer. We report the synthesis of multifunctional theranostic SP94-modified polypyrrole (PPy)-BSA-ICG nanoparticles by a simple method. The multifunctional theranostic agent helped to combine two modes of imaging modalities, i.e. photoacoustic and near infrared (NIR) fluorescence imaging, together with photothermal therapy. These nanoparticles exhibited an excellent stability in physiological solutions (PBS, pH 7.4 at 37 °C), a higher tumor accumulation as compared to the unmodified nanoparticles, and minimal nonspecific uptake by other normal organs such as liver and spleen. Most importantly, the nanoparticles could effectively kill the tumor through photothermal therapy with no tumor recurrence upon a single laser irradiation event. These results indicate that SP94-modified PPy-BSA-ICG is potentially a promising theranostic agent for image-guided cancer therapy as it overcomes the limitations of each of the imaging modalities and thus improves the therapeutic efficiency and reduces the side effects.


Subject(s)
Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Nanoparticles/chemistry , Phototherapy , Polymers/chemistry , Pyrroles/chemistry , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Cell Line, Tumor , Human Umbilical Vein Endothelial Cells , Humans , Liver Neoplasms/diagnostic imaging , Male , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/diagnostic imaging , Neoplasms, Experimental/therapy , Optical Imaging , Theranostic Nanomedicine
17.
Bioconjug Chem ; 29(4): 1475-1484, 2018 04 18.
Article in English | MEDLINE | ID: mdl-29544252

ABSTRACT

In clinical imaging modalities, MRI is suitable for preoperative examination. Fluorescence imaging has been proposed to improve the detectability of cancer lesions during the operation. However, the specificity and accuracy of the two imaging modalities is limited. To improve the prognosis and survival rate of the patient suffering from hepatocellular carcinoma (HCC), it is very important to develop a specific probe to achieve early detection and precise resection of HCC. We selected HCC targeting peptide SP94 to conjugate with a NIR dye and Gd chelated DOTA to enhance the specificity of different imaging modalities. MRI and fluorescence imaging were used for preoperative examination of the cancer and detecting the tumor in the operation, respectively. MRI and fluorescence signals significantly increased when HCC occurs and the obtained probe shows high uptake in HCC but negligible uptake in the normal liver tissues. The signal-to-background ratio is higher than 2.23 (MRI) and 2.0 (fluorescence imaging) with noninvasive imaging modalities. After the intraperitoneal cavity was surgically exposed, the signal-to-background ratio is higher than 4.6. By combining the high specificity of our probe with the high sensitivity of fluorescence imaging, the microprimary malignancy and micrometastasis foci (diameter <1 mm) can be easily detected after the intraperitoneal cavity is exposed. These results indicated that our probe is conductive to the early detection and precise resection of the HCC and has the potential to improve the diagnosis and treatment of patients with HCC.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Coloring Agents/chemistry , Contrast Media/chemistry , Gadolinium/chemistry , Heterocyclic Compounds, 1-Ring/chemistry , Liver Neoplasms/diagnostic imaging , Peptides/chemistry , Animals , Hep G2 Cells , Humans , Infrared Rays , Magnetic Resonance Imaging/methods , Mice, Inbred BALB C , Mice, Nude , Optical Imaging/methods , Preoperative Period
18.
Cancer Lett ; 397: 61-71, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28351615

ABSTRACT

Early detection and therapy of esophageal cancer is very important for improving the prognosis and survival rate of the patient. A theranostic agent that combines multimodal imaging with cancer therapy may be used for augmenting the visualization and treatment of the cancer. Herein, we report the synthesis of a hollow tantalum oxide (TaOx) nanoparticle that was successfully engineered by encapsulation of polypyrrole (PPy) and doxorubicin (DOX) in the core and conjugation with a near infrared fluorescence dye (NIRDye800) on the shell of the hollow TaOx nanoparticles. The as-prepared core/shell nanoparticles showed multimodal imaging features including computed tomography (CT) (for the preliminary location of the tumor), photoacoustic (for the anatomical localization of the tumor), and fluorescence imaging (for real-time monitoring of the tumor margin) and pH- and thermal-sensitive drug release. Because the early esophageal carcinoma is a type of superficial cancer, a subcutaneous model in the thigh was used for the in vivo study. The core/shell nanoparticles shows high imaging contrast between the tumor and the adjacent tissues and controllable photothermal therapy (PTT) and chemotherapy. Our results indicated that the obtained core/shell nanoparticles had significant potential in the triple-modality imaging guided precisely chemo-thermal synergetic therapy of esophageal cancer. In addition, after aerosol administration, our nanoparticles also exhibited comparable therapeutic efficacy with the intravenous administration, which is more suitable for clinical therapy of esophageal carcinoma.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carcinoma/diagnostic imaging , Carcinoma/therapy , Contrast Media/administration & dosage , Doxorubicin/administration & dosage , Drug Carriers , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapy , Fluorescent Dyes/administration & dosage , Multimodal Imaging/methods , Nanoparticles , Oxides/administration & dosage , Phototherapy/methods , Tantalum/administration & dosage , Animals , Antibiotics, Antineoplastic/chemistry , Carcinoma/pathology , Cell Line, Tumor , Contrast Media/chemistry , Doxorubicin/chemistry , Drug Liberation , Esophageal Neoplasms/pathology , Fluorescent Dyes/chemistry , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/pathology , Humans , Hydrogen-Ion Concentration , Male , Mice, Inbred BALB C , Optical Imaging , Oxides/chemistry , Photoacoustic Techniques , Polymers/chemistry , Predictive Value of Tests , Pyrroles/chemistry , Solubility , Tantalum/chemistry , Temperature , Theranostic Nanomedicine , Time Factors , Tomography, X-Ray Computed , Xenograft Model Antitumor Assays
19.
Bioconjug Chem ; 27(12): 2931-2942, 2016 Dec 21.
Article in English | MEDLINE | ID: mdl-27998076

ABSTRACT

The microwave and temperature sensitive liposomes were fabricated successfully from 1,2-dipalmityol-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000) with a molar ratio of 4:1:0.26 by co-encapsulating NaCl and doxorubicin (DOX) through the thin-film hydration method to externally manipulate drug release at a predetermined location in the body at a desired time in the right dosage for combination microwave hyperthermia and chemotherapy of cancer to afford a synergistic therapeutic effect. It was found that the confinement of the high concentration of NaCl ions inside the small size of the liposomes led to a more-rapid temperature elevation than the dissociative ions upon microwave treatment. More than 67.6% doxorubicin was released from the DOX and NaCl co-loaded liposomes (DOX&NaCl@liposomes) upon microwave irradiation for 2 min. After incubation with 2 mg/mL DOX&NaCl@liposomes for 4 h followed by treatment with microwave for 2 min, the inhibition rate of human breast cancer cell MDA-MB-231 was evaluated as 76.1%, much higher than that for NaCl@liposomes (29.8%) and DOX@liposomes (40.2%). The tumor growth inhibition was evaluated to be 73.4% after intravenous injection of DOX&NaCl@liposomes followed by microwave irradiation, much higher than that with only NaCl@liposomes (41.5%) or DOX@liposomes (45.5%) combined with microwave irradiation. Therefore, DOX&NaCl@liposomes could serve as a promising thermochemotherapy nanomedicine for cancer treatment because of its excellent microwave susceptible property and good biocompatibility.


Subject(s)
Breast Neoplasms/therapy , Doxorubicin/pharmacokinetics , Hyperthermia, Induced/methods , Liposomes/chemistry , Sodium Chloride/chemistry , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Breast Neoplasms/drug therapy , Doxorubicin/administration & dosage , Drug Liberation , Female , Hemolysis/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Liposomes/administration & dosage , Liposomes/pharmacokinetics , Mice, Inbred BALB C , Mice, Nude , Microwaves , Xenograft Model Antitumor Assays
20.
Cancer Biol Med ; 13(3): 349-359, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27807502

ABSTRACT

Objective: Photoacoustic (PA) tomography (PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body. Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy (polyethylene glycol)] (DSPE-PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs) loaded with indocyanine green (ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals. Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which the in vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting. Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications.

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