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1.
Int J Nanomedicine ; 15: 5017-5026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764933

RESUMO

Background: Molecular imaging is of great benefit to early disease diagnosis and timely treatment. One of the most striking innovations is the development of multimodal molecular imaging technology, which integrates two or more imaging modalities, largely in view of making the best of the advantages of each modality while overcoming their respective shortcomings. Hence, engineering a versatile and easily prepared nanomaterial with integrating multimodal molecular imaging function holds great promise, but is still a great challenge. Materials and Methods: We firstly designed and synthesized a BDT-DPP conjugated polymer and then noncovalent self-assembly with phospholipid-polyethylene glycol endowed BDT-DPP with water solubility and biocompatibility. Followed by [Cu] labeling, the acquired multifunctional nanoparticles (NPs) were studied in detail for the photophysical property. The cytotoxicity and biocompatibility of DPP-BDT NPs were examined through MTT assay and H&E stained analysis. In addition, we investigated the accumulation of the NPs in HepG2 tumor models by positron emission tomography (PET) and photoacoustic (PA) dual-mode imaging. Results and Discussion: The DPP-BDT NPs exhibited excellent optical stability, strong near-infrared (NIR) light absorption as well as fine biocompatibility. After tail vein injection into the living mice, the PA signals in the neoplastic tissues were gradually increased and reached to the maximum at the 4-h post-injection, which was consistent with the PET analysis. Such strong PA and PET signals were attributed to the efficient NPs accumulation resulting from the enhanced permeability and retention (EPR) effect. Conclusion: The biocompatible DPP-BDT NPs demonstrated to be strong NIR absorption property and PAI sensitivity. Besides, these novel DPP-BDT NPs can act not only as a PA imaging contrast agent but also as an imaging agent for PET.

3.
Nanoscale ; 12(29): 15845-15856, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32696787

RESUMO

Although nanomedicines have shown high performance in tumor theranostics, their anticancer activity is still limited by the drug delivery capacity, especially lack of targeting capability, poor tumor accumulation, and insufficient tumor deep-penetration. To address this challenge, a high biocompatibility nano-truck (BMP NT) with a two-stage delivery mechanism is designed and developed to achieve the precision therapeutic efficacy of cancer. In view of the enhanced permeability retention (EPR) effect, the surface cleavable layer of BMP NTs can be selectively removed by the overexpressed MMP-2 in a tumor-microenvironment to expose the hydrophobic segments for an induced "braking effect" strategy, resulting in a significant increase in tumor accumulation. Once internalized into cancer cells with the overproduced glutathione (GSH) and H2O2, the BMP NTs undergo the second-stage "unloading process" to release Mn2+ ions and ultrasmall Bi2S3@BSA nanoparticles, and the obtained Mn2+ ions can act as a Fenton-like catalyst for continuously catalyzing the endogenous H2O2 into highly toxic hydroxyl radicals (˙OH) for CDT. The GSH depletion will in turn improve the Mn2+-H2O2 reaction, further enhancing CDT efficiency. Meanwhile, the ultrasmall Bi2S3@BSA endows BMP NTs with excellent photothermal conversion ability to generate local hyperthermia and accelerate the intratumoral Fenton process, thus leading to an effective tumor therapeutic outcome in the synergistic function of CDT/photothermal therapy (PTT). Moreover, the BMP NTs can be used for in situ self-generation magnetic resonance imaging (MRI) and photoacoustic (PA) imaging to guide precision cancer therapy.

4.
J Inorg Biochem ; 209: 111121, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32505013

RESUMO

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window exhibits enhanced deep-tissue imaging capability. Likely, cancer therapy in the NIR-II window could provide deeper penetration depth and higher exposure to laser over NIR-I. However, the traditional application of excitation light is still in the NIR-I window. In view of the excellent imaging and therapeutic capabilities of NIR-II window, we have demonstrated a simple polyoxometalate (POM) clusters (molecular formula: (Na)n(PMo12O40) or (NH4+)n(PMo12O40)), which integrates NIR-II photoacoustic imaging and NIR-II photothermal therapy into an "all-in-one" theranostic nanoplatform, and could be used for PA imaging-guided photothermal therapy in the NIR-II window. In vivo experiments demonstrate that the POM clusters with good water solubility and biocompatibility were effective to kill tumor without recurrence and metastasis under 1064 nm laser illumination.

5.
Nanomedicine ; 29: 102248, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32574686

RESUMO

Melanin is a group of natural pigments found in living organism. It can be used for positron emission tomography (PET) imaging due to its inherent chelating ability to radioactive cupric ion. This study was to prepare 64Cu-labeled PEGylated melanin nanoparticles (64Cu-PEG-MNPs), and to further take advantage of the enhanced permeability and retention (EPR) effect of radiolabeled nanoparticles to realize the integration of tumor diagnosis and treatment. We successfully synthesized PEG-MNPs. Saline and serum stability experiments demonstrated good stability. PET/CT showed high tumor aggregation. Moreover, 64Cu-PEG-MNPs resulted in a therapeutic effect on the A431 tumor-bearing mice in the treatment group. The pathological results further confirmed that the therapeutic doses of 64Cu-PEG-MNPs cause pathological changes of tumor tissues while showing minimal toxicity to normal tissues. Our data successfully demonstrate the good imaging performance of 64Cu-PEG-MNPs on A431 tumors and further proved its therapeutic effect, highlighting a great potential in targeted radionuclide therapy.

6.
Nanoscale ; 12(21): 11562-11572, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32432283

RESUMO

Nanosystems responsive to a tumor microenvironment (TME) have recently attracted great attention due to their potential in precision cancer theranostics. However, theranostic nanosystems with a TME-activated consecutive cascade for the accurate diagnosis and treatment of cancer have rarely been exploited. Herein, an activatable theranostic nanosystem (Bi2S3-Ag2S-DATS@BSA-N3 NYs) is designed and constructed on the basis of a one-pot biomineralization method and surface functional modification to improve second near-infrared (NIR-II) fluorescence/photoacoustic (PA) imaging-guided photothermal therapy (PTT)/gas therapy (GT). Based on enhanced penetration and retention (EPR) effect-mediated tumor accumulation, the tumor-overexpressed glutathione (GSH) can accelerate hydrogen sulfide (H2S) generation from the nanoparticles by reacting with the encapsulated diallyl trisulfide (DATS). Meanwhile, the in situ released H2S can be used not only for gas therapy, but also to start the reduction of -N3(-) to -NH2(+), thereby enhancing the tumor-specific aggregation of NYs. As a result, the activatable nanosystems with excellent tumor accumulation and biodistribution could achieve an accurate NIR-II/PA dual-modality imaging for guiding the synergistic anticancer efficacy (PTT/GT). Thus, this work provides a promising TME-mediated continuously responsive strategy for efficient anticancer therapy.

7.
Nat Commun ; 11(1): 1857, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312987

RESUMO

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.


Assuntos
Ferro/uso terapêutico , Neoplasias/patologia , Neoplasias/terapia , Fototerapia/métodos , Polímeros/química , Semicondutores , Animais , Apoptose , Catálise , Linhagem Celular Tumoral , Quelantes , Ferroptose , Células HeLa , Humanos , Peróxido de Hidrogênio , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Camundongos , Microscopia Confocal , Células NIH 3T3 , Nanomedicina/métodos , Nanopartículas/química , Metástase Neoplásica , Neoplasias/metabolismo , Oxigênio/química , Técnicas Fotoacústicas , Ratos , Espécies Reativas de Oxigênio/metabolismo
8.
Anal Chim Acta ; 1109: 44-52, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32252904

RESUMO

The development of quantitative metabolomics approaches for future standardized and translational applications has become increasingly important. Data-independent targeted quantitative metabolomics (DITQM) is a newly proposed method providing ion pair information on 1324 metabolites. However, the quantification of more than 1000 metabolites in large sample sizes has still not been implemented. In this study, on the basis of the DITQM concept, scheduled multiple reaction monitoring (MRM) methods for both high-abundant and low-abundant metabolites were established to broaden the quantification coverage, and an open-source program "Quanter_1.0" was coded to facilitate efficient data handling. Our results demonstrated that 1015 metabolites in human plasma met the quantitative requirements and could be relatively determined in an effective manner. The method was then applied to a large-scale sample study of lung cancer consisting of three distinct analytical batches. It was obvious that data quality that originated from quantitative metabolomics was improved, with substantially lower intra- and inter-batch data variation, resulting in a more effective multivariate statistical model. Finally, 26 potential biomarkers of lung cancer were discovered. Collectively, our approach provides a promising tool for quantitative metabolomics research involving large-scale sample sizes and clinical application.

9.
Head Neck ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32323895

RESUMO

BACKGROUND: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. METHODS: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. RESULTS: Niraparib reduced colony formation in two of the four cell lines tested (P < .05), enhanced radiosensitivity in all four cell lines, delayed DDR (P < .05), and increased proton vs photon RBE. CONCLUSION: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.

10.
Sci Rep ; 10(1): 7493, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32346120

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

11.
Theranostics ; 10(6): 2621-2630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194824

RESUMO

The development of improved or targeted drugs that discriminate between normal and tumor tissues is the key therapeutic issue in cancer research. However, the development of an analytical method with a high accuracy and sensitivity to achieve quantitative assessment of the tumor targeting of anticancer drugs and even intratumor heterogeneous distribution of these drugs at the early stages of drug research and development is a major challenge. Mass spectrometry imaging is a label-free molecular imaging technique that provides spatial-temporal information on the distribution of drugs and metabolites in organisms, and its application in the field of pharmaceutical development is rapidly increasing. Methods: The study presented here accurately quantified the distribution of paclitaxel (PTX) and its prodrug (PTX-R) in whole-body animal sections based on the virtual calibration quantitative mass spectrometry imaging (VC-QMSI) method, which is label-free and does not require internal standards, and then applied this technique to evaluate the tumor targeting efficiency in three treatment groups-the PTX-injection treatment group, PTX-liposome treatment group and PTX-R treatment group-in nude mice bearing subcutaneous A549 xenograft tumors. Results: These results indicated that PTX was widely distributed in multiple organs throughout the dosed body in the PTX-injection group and the PTX-liposome group. Notably, in the PTX-R group, both the prodrug and metabolized PTX were mainly distributed in the tumor tissue, and this group showed a significant difference compared with the PTX-liposome group, the relative targeting efficiency of PTX-R group was increased approximately 50-fold, leading to substantially decreased systemic toxicities. In addition, PTX-R showed a significant and specific accumulation in the poorly differentiated intratumor area and necrotic area. Conclusion: This method was demonstrated to be a reliable, feasible and easy-to-implement strategy to quantitatively map the absorption, distribution, metabolism and excretion (ADME) of a drug in the whole-body and tissue microregions and could therefore evaluate the tumor-targeting efficiency of anticancer drugs to predict drug efficacy and safety and provide key insights into drug disposition and mechanisms of action and resistance. Thus, this strategy could significantly facilitate the design and optimization of drugs at the early stage of drug research and development.

12.
Anal Chem ; 92(7): 5143-5151, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32134635

RESUMO

2-Hydroxy fatty acids (2-OHFAs) and 3-hydroxy fatty acids (3-OHFAs) with the same carbon backbone are isomers, both of which are closely related to diseases involving fatty acid oxidation disorder. However, the comprehensive profiling of 2- and 3-OHFAs remains an ongoing challenge due to their high structure similarity, few structure-informative product ions, and limited availability of standards. Here, we developed a new strategy to profile and identify 2- and 3-OHFAs according to structure-dependent retention time prediction models using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Both accurate MS and MS/MS spectra were collected for peak annotation by comparison with an in-house database of theoretically possible 2- and 3-OHFAs. The structures were further confirmed by the validated structure-dependent retention time prediction models, taking advantage of the correlation between the retention time, carbon chain length and number of double bonds, as well as the hydroxyl position-induced isomeric retention time shift rule. With the use of this strategy, 18 2-OHFAs and 32 3-OHFAs were identified in the pooled plasma, of which 7 2-OHFAs and 20 3-OHFAs were identified for the first time in this work, furthering our understanding of OHFA metabolism. Subsequent quantitation method was developed by scheduled multiple reaction monitoring (MRM) and then applied to investigate the alteration of 2- and 3-OHFAs in esophageal squamous cell carcinoma (ESCC) patients. Finally, a potential biomarker panel consisting of six OHFAs with good diagnostic performance was achieved. Our study provides a new strategy for isomer identification and analysis, showing great potential for targeted metabolomics in clinical biomarker discovery.

13.
Sci Rep ; 10(1): 5511, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218504

RESUMO

To evaluate the role of conventional contrast-enhanced CT (CECT) imaging and dual-energy spectral CT (DECT) perfusion imaging in differentiating the WHO histological subtypes of thymic epithelial tumours (TETs). Eighty-eight patients with TETs who underwent DECT perfusion scans (n = 51) and conventional CT enhancement scans (n = 37) using a GE Discovery CT750 HD scanner were enrolled in this study. The mean maximal contrast-enhanced range (mean CEmax) and the perfusion and spectral parameters of the lesions were analysed. Among the six WHO subtypes (Type A, AB, B1, B2, and B3 thymoma and thymic carcinoma), the mean CEmax values and most of the perfusion and spectral parameter values of Type A and Type AB were significantly higher than those of the other subtypes (all P < 0.05), and there was no difference among Type B1, B2 and B3 (all P > 0.05). The mean CEmax value was not different between Type B (including Type B1, B2, and B3) and thymic carcinoma (P = 1.000). The PS, IC, NIC and λHU values in the optimal venous phase of thymic carcinoma were higher than those of Type B (all P < 0.05). The parameters of conventional CECT imaging and DECT perfusion imaging can help identify the subtype of TETs, especially those of DECT perfusion imaging in type B thymomas and thymic carcinomas.

14.
Head Neck ; 42(2): 289-301, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710172

RESUMO

BACKGROUND: Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear. METHODS: Proteomics analyses of protein expression profiles by reverse-phase protein arrays were done for two human papillomavirus [HPV]-negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested. RESULTS: Compared with PRT, XRT tended to induce lower expression of DNA damage repair-and cell cycle arrest-related proteins and higher expression of cell survival- and proliferation-related proteins. CONCLUSIONS: Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.

15.
Biomater Sci ; 8(1): 379-390, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31728481

RESUMO

Melanin nanoparticles are of great importance in biomedicine. They have excellent affinity for metallic cations, especially paramagnetic ions, which has sparked interest in their application in the development of magnetic resonance imaging (MRI) contrast agents. In this work, we prepared ultrasmall water-soluble melanin nanoparticles, and investigated the binding properties of melanin toward different metal cations (Gd3+, Mn2+, Fe3+ and Cu2+), and compared their physicochemical properties and the MRI contrast enhancement ability in various metal chelated forms (MNP-PEG-M) in vitro and in vivo. We show that the saturation binding numbers of Gd3+, Mn2+, Fe3+ and Cu2+ per MNP-PEG were 49, 59, 69 and 62, respectively. MNP-PEG-Gd, MNP-PEG-Mn, MNP-PEG-Fe and MNP-PEG-Cu exhibited the maximum r1 relaxivities at the loading mass ratios of Gd3+ : MNP = 1 : 1, Mn2+ : MNP = 0.5 : 1, Fe3+ : MNP = 0.1 : 1 and Cu2+ : MNP = 0.1 : 1, corresponding to 49, 57, 54 and 51 chelated metals per MNP-PEG, respectively. The maximal per metal ion r1 relaxivity values were 61.9, 48.7, 11.1 and 9.7 mM-1 s-1 for MNP-PEG-Gd, MNP-PEG-Mn, MNP-PEG-Fe and MNP-PEG-Cu at 1.5 T, respectively. MNP-PEG-Gd and MNP-PEG-Fe presented larger sizes (6.9 nm and 5.8 nm) than MNP-PEG-Mn and MNP-PEG-Cu (3.4 nm and 3.7 nm), all featuring excellent solubility, high stability and ultrasmall size. A significant in vivo MRI signal enhancement in tissues was observed for all MNP-PEG-M after intravenous injection in mice, and these nanoparticles were excreted through renal and hepatobiliary pathways. In agreement with their r1 relaxivity values, MNP-PEG-Gd and MNP-PEG-Mn showed a significantly greater in vivo tissue maximum enhancement than MNP-PEG-Fe and MNP-PEG-Cu. This study could yield valuable insight into the development of a new class of MRI contrast agents.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética/métodos , Melaninas/química , Metais/química , Nanopartículas/química , Animais , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Compostos Férricos/química , Gadolínio/química , Íons/química , Rim/diagnóstico por imagem , Rim/metabolismo , Rim/patologia , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Manganês/química , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Polietilenoglicóis/química , Ratos , Distribuição Tecidual
16.
Nanoscale ; 12(2): 548-557, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793608

RESUMO

Hypoxia is known to be a common feature within many types of solid tumors, which is closely related to the limited efficacy of radiotherapy. Meanwhile, due to the non-discriminatory killing effect of both normal and cancer cells during the radiation process, traditional radiosensitizers could bring severe non-negligible side-effects to the whole body. In this work, stable and atomically precise Mn clusters which possess efficient pH-triggered catalytic selective capacity are developed rationally. Mn clusters could efficiently catalyze oxygen production in an acidic tumor microenvironment, while exhibiting strong reducibility and free radical scavenging ability in neutral circumstances. In vivo experiments show that Mn clusters are able to enhance the radiotherapy effect in the mouse model of 4T1 tumors and protect normal tissues from radiation at the same time. Thus, the present work provides a novel dual-functional strategy to enhance radiotherapy-induced tumor treatment by improving tumor oxygenation and protect normal tissues from radiation simultaneously.

17.
Adv Mater ; 32(6): e1906314, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833600

RESUMO

Real-time in vivo imaging of immunoactivation is critical for longitudinal evaluation of cancer immunotherapy, which, however, is rarely demonstrated. This study reports semiconducting polymer nanoreporters (SPNRs) with superoxide anion (O2 •- )-activatable chemiluminescence signals for in vivo imaging of immunoactivation during cancer immunotherapy. SPNRs are designed to comprise an SP and a caged chemiluminescence phenoxy-dioxetane substrate, which respectively serve as the chemiluminescence acceptor and donor to enable intraparticle chemiluminescence resonance energy transfer. SPNRs are intrinsically fluorescent but only become chemiluminescent upon activation by O2 •- . Representing the first O2 •- -activatable near-infrared chemiluminescent reporter, SPNR3 sensitively differentiates higher O2 •- levels in immune cells from other cells including cancer and normal cells. Following systemic administration, SPNR3 passively accumulates into tumors in living mice and activates the chemiluminescence signals responding to the concentration of O2 •- in the tumor microenvironment. Moreover, the enhancement of in vivo chemiluminescence signal after cancer immunotherapy is correlated with increased population of T cells in the tumor, proving its feasibility in tracking of T cell activation. Thus, SPNRs represent the first kind of chemiluminescent reporters competent for in vivo imaging of immunoactivation.

18.
Chem Sci ; 10(36): 8348-8353, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31803412

RESUMO

Small-molecule based multifunctional probes play significant roles in biomedical science and possess high clinical translational ability. However, the preparation of these promising probes without complicated synthetic procedures remains a challenging task. Herein, we rationally designed a high-performance DD-A-DD scaffold molecular dye (SYL) with an intrinsic multifunctional ability and then incorporated it into DSPE-mPEG5000 to facilely construct biocompatible NIR-II fluorescent and photoacoustic (PA) dual-modal theranostic nanoprobes (SYL NPs) (∼120 nm). In vivo studies confirmed that SYL NPs exhibited bright NIR-II fluorescence and PA signals in the tumor region with a promising signal to background ratio (S/B). Meanwhile, SYL NPs demonstrated significantly inhibited tumor growth under laser irradiation with no noticeable side effects. These promising results highlighted SYL NPs as a potential theranostic platform for cancer diagnosis (NIR-II region) and therapy.

19.
ACS Nano ; 13(12): 13843-13852, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31697475

RESUMO

Compared with photon-induced binary cancer therapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), boron neutron capture therapy (BNCT) emerges as an alternative noninvasive treatment strategy that could overcome the shallow penetration of light. One key factor in performing successful BNCT is to accumulate a sufficient amount of B-10 (>20 ppm) within tumor cells, which has been a long-standing challenge for small-molecule-based boron drugs. Boron nitride nanoparticles (BNNPs) are promising boron carriers due to their high boron content and good biocompatibility, as certain types of BNNPs can undergo rapid degradation under physiological conditions. To design an on-demand degradable boron carrier, BNNPs were coated by a phase-transitioned lysozyme (PTL) that protects BNNPs from hydrolysis during blood circulation and can be readily removed by vitamin C after neutron capture therapy. According to PET imaging, the coated BNNPs exhibited high tumor boron accumulation while maintaining a good tumor to nontumor ratio. Tail-vein injections of vitamin C were followed by neutron irradiation, and BNNPs were found to be rapidly cleared from major organs according to ex vivo ICP-OES analysis. Compared with the control group, animals treated with BNCT showed suppression of tumor growth, while almost negligible side effect was observed. This strategy not only utilized the high boron content of BNNPs but also successfully performed an on-demand degradation of BNNPs to avoid the potential toxicity caused by the long-term accumulation of nanoparticles.

20.
Eur J Radiol ; 121: 108735, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31733432

RESUMO

PURPOSE: The study is to explore potential features and develop classification models for distinguishing benign and malignant lung lesions based on CT-radiomics features and PET metabolic parameters extracted from PET/CT images. MATERIALS AND METHODS: A retrospective study was conducted in baseline 18 F-flurodeoxyglucose positron emission tomography/ computed tomography (18 F-FDG PET/CT) images of 135 patients. The dataset was utilized for feature extraction of CT-radiomics features and PET metabolic parameters based on volume of interest, then went through feature selection and model development with strategy of five-fold cross-validation. Specifically, model development used support vector machine, PET metabolic parameters selection used Akaike's information criterion, and CT-radiomics were reduced by the least absolute shrinkage and selection operator method then forward selection approach. The diagnostic performances of CT-radiomics, PET metabolic parameters and combination of both were illustrated by receiver operating characteristic (ROC) curves, and compared by Delong test. Five groups of selected PET metabolic parameters and CT-radiomics were counted, and potential features were found and analyzed with Mann-Whitney U test. RESULTS: The CT-radiomics, PET metabolic parameters, and combination of both among five subsets showed mean area under the curve (AUC) of 0.820 ±â€¯0.053, 0.874 ±â€¯0.081, and 0.887 ±â€¯0.046, respectively. No significant differences in ROC among models were observed through pairwise comparison in each fold (P-value from 0.09 to 0.81, Delong test). The potential features were found to be SurfaceVolumeRatio and SUVpeak (P < 0.001 of both, U test). CONCLUSION: The classification models developed by CT-radiomics features and PET metabolic parameters based on PET/CT images have substantial diagnostic capacity on lung lesions.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Área Sob a Curva , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Máquina de Vetores de Suporte
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