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1.
Bioconjug Chem ; 35(6): 843-854, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38775802

RESUMO

The prevalence and fatality rates of gastric cancer (GC) remain elevated, with advanced stages presenting a grim prognosis. Noninvasive diagnosis of GC cancer often proves challenging until the disease has progressed to an advanced stage or metastasized. Initially, the level of fibronectin (FN) in cancer-associated fibroblasts (CAFs) of GC was at least 3.7 times higher than that in normal fibroblasts. Herein, two FN-targeting magnetic resonance/near-infrared fluorescence (MR/NIRF) imaging contrast agents were developed to detect GC and peritoneal metastasis noninvasively. The probes CREKA-Cy7-(Gd-DOTA) and CREKA-Cy7-(Gd-DOTA)3 demonstrated significant FN-targeting capability (with dissociation constants of 1.0 and 2.1 mM) and effective MR imaging performance (with proton relaxivity values of 9.66 and 27.44 mM-1 s-1 at 9.4 T, 37 °C). In vivo imaging revealed a high signal-to-noise ratio and successful visualization of GC metastasis using NIRF imaging as well as successful tumor detection in MR imaging. Therefore, this study highlights the potential of FN-targeting probes for GC diagnosis and aids in the advancement of new diagnostic strategies for the clinical detection of GC.


Assuntos
Meios de Contraste , Fibronectinas , Imageamento por Ressonância Magnética , Neoplasias Peritoneais , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Fibronectinas/metabolismo , Imageamento por Ressonância Magnética/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico , Humanos , Meios de Contraste/química , Animais , Camundongos , Imagem Óptica/métodos , Compostos Organometálicos/química , Linhagem Celular Tumoral , Compostos Heterocíclicos
2.
Acad Radiol ; 30 Suppl 1: S230-S237, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37453883

RESUMO

RATIONALE AND OBJECTIVES: Pancreatic fibrosis is the hallmark of chronic pancreatitis (CP), which is associated with microcirculatory disturbance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess the perfusion and permeability of the pancreas by providing information about microcirculation. We hypothesize that DCE-MRI parameters can be utilized to assess pancreatic fibrosis and may furthermore provide an opportunity to evaluate response to antifibrotic treatment with curcumin. Our study was to evaluate the feasibility of quantitative DCE-MRI in assessing pancreatic fibrosis and the antifibrotic effect of curcumin in a rat model of CP. MATERIALS AND METHODS: Pancreatic fibrosis was induced by injecting dibutyltin dichloride (DBTC). Seventy rats were randomized to five groups: the control group (n = 10); DBTC for 2 weeks (n = 15); DBTC for 4 weeks (n = 15); DBTC + curcumin for 2 weeks (n = 15); DBTC + curcumin for 4 weeks (n = 15). DCE-MRI was performed at an 11.7 T MR scanner. DCE-MRI quantitative parameters (Ktrans, Ve, and Vp) were derived from an extended Tofts model. Fibrosis content and DCE-MRI parameters were compared among the above groups (one-way analysis of variance). The correlations between DCE-MRI parameters and pancreatic fibrosis content as well as the expression of α-SMA were computed by Spearman correlation coefficients. RESULTS: Fifty-three rats survived and underwent MR imaging. Ktrans in rats 4 weeks after DBTC injection was significantly lower than DBTC 2 weeks rats and control rats (0.30 ± 0.06 min vs 0.49 ± 0.09 vs 0.62 ± 0.09, respectively). Vp in DBTC 4 weeks rats was also significantly lower than control rats (0.048 ± 0.010 min-1 vs 0.065 ± 0.011 min-1, respectively). Ktrans and Vp significantly correlated with fibrosis content of pancreas (r = -0.619 and -0.450, all P < 0.001), and the expression of α-SMA (r = -0.688 and -0.402, all P < 0.01). Ktrans and Vp in rats with daily curcumin treatment for 4 weeks were significantly higher than DBTC 4 weeks rats (Ktrans, 0.51 ± 0.09 vs 0.30 ± 0.06; Vp, 0.064 ± 0.015 vs 0.048 ± 0.010). CONCLUSION: DCE-MRI parameters (Ktrans and Vp) have the potential to noninvasively assess pancreatic fibrosis and the antifibrotic treatment response of curcumin.


Assuntos
Curcumina , Animais , Ratos , Meios de Contraste , Curcumina/farmacologia , Curcumina/uso terapêutico , Fibrose , Imageamento por Ressonância Magnética/métodos , Microcirculação
3.
Biomaterials ; 292: 121920, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36442436

RESUMO

Despite the success of immune checkpoint blockade (ICB) therapy in cancer management, ICB-based immunotherapy of triple-negative breast cancer (TNBC) still suffers from immunosuppressive tumor microenvironment (ITM). To break through the bottleneck of TNBC immunotherapy, a self-cascaded unimolecular prodrug consisting of an acidic pH-activatable doxorubicin and an aggregation-induced emission luminogen (AIEgen) photosensitizer coupled to a caspase-3-responsive peptide was engineered. The generated prodrug, could not only release doxorubicin initiatively in acidic tumor microenvironment, but also activate apoptosis-related caspase-3. The activated caspase-3 could in turn trigger release and in situ aggregation of photosensitizers. Importantly, the unimolecular prodrug exhibits a renal clearance pathway similar to small molecules in vivo, while the aggregated AIEgens prolong tumor retention for long-term fluorescence imaging and repeatable photodynamic therapy (PDT) by only one single-dose injection. Furthermore, the tumor-detained PDT boosts both immunogenic cell death of TNBC cells and maturation of dendritic cells. Finally, the combination of repeatable PDT with ICB therapy further promotes the proliferation and intratumoral infiltration of cytotoxic T lymphocytes, and effectively suppresses tumor growth and pulmonary metastasis. This prodrug is a proof-of-concept that confirms the first self-cascaded chemo-PDT strategy to reverse the ITM and boost the ICB-mediated TNBC immunotherapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Pró-Fármacos , Neoplasias de Mama Triplo Negativas , Humanos , Pró-Fármacos/uso terapêutico , Pró-Fármacos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Caspase 3 , Imunoterapia/métodos , Fármacos Fotossensibilizantes/química , Microambiente Tumoral , Doxorrubicina/farmacologia , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Nanopartículas/química
4.
J Magn Reson Imaging ; 55(2): 507-517, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34254388

RESUMO

BACKGROUND: T1, T2, and T1ρ might be potential biomarkers for assessing liver fibrosis. However, few studies reported the value of them in different animal models. PURPOSE: To investigate and compare the performances of T1, T2, and T1ρ for noninvasively staging liver fibrosis in bile duct ligation (BDL) or carbon tetrachloride (CCl4 ) model. STUDY TYPE: Prospective animal model. SUBJECTS: Liver fibrosis was induced by BDL or injection of CCl4 in 120 rats. FIELD STRENGTH/SEQUENCE: 11.7 T, T1 mapping with 10 repetition times, T2 mapping with 32 echo times, and T1ρ with 10 spin-lock times. ASSESSMENT: T1, T2, and T1ρ were measured and correlated with liver fibrosis stages, as well as the degree of inflammation, steatosis, iron deposition, and the expression of cytokeratin 19. The discriminative performance of T1, T2, and T1ρ for staging liver fibrosis was compared. STATISTICAL TESTS: One-way analysis of variance (ANOVA), Spearman's correlation analysis, factorial design ANOVA, and receiver operating characteristic curves (P < 0.05 was considered statistically significant). RESULTS: T1, T2, and T1ρ (BDL: rho = 0.73, 0.85, 0.68; CCl4 : rho = 0.80, 0.29, 0.61) were significantly correlated with liver fibrosis stages, while there was no significant difference in T2 among stage F0-F4 in the CCl4 model (P = 0.204). The area under the curves (AUCs) range of T1, T2, and T1ρ for predicting ≥F1, ≥F2, ≥F3, and F4 were 0.76-0.95, 0.89-0.98, and 0.80-0.94 in the CCl4 model. For the CCl4 model, the AUCs range of T1, T2, and T1ρ for predicting ≥F1, ≥F2, ≥F3, and F4 were 0.83-0.95, 0.61-0.74, and 0.73-0.89, respectively. T2 had significantly higher AUC in the BDL model than CCl4 model for diagnosing liver fibrosis. DATA CONCLUSION: The most sensitive and accurate method for staging liver fibrosis appeared to be T1 in our animal models followed by T1ρ. T2 may not be suitable for evaluating liver fibrosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.


Assuntos
Tetracloreto de Carbono , Cirrose Hepática , Animais , Ductos Biliares/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Ratos
5.
Chem Sci ; 12(29): 10063-10069, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34349970

RESUMO

The use of peptide amphiphiles (PAs) is becoming increasingly popular, not only because of their unique self-assembly properties but also due to the versatility of designs, allowing biological responsiveness, biocompatibility, and easy synthesis, which could potentially contribute to new drug design and disease treatment concepts. Oligonucleotides, another major functional bio-macromolecule class, have been introduced recently as new functional building blocks into PAs, further enriching the tools available for the fabrication of bio-functional PAs. Taking advantage of this, in the present work, two nucleic base-linked (adenine, A and thymine, T) RGD-rich peptide amphiphiles (NPAs) containing the fluorophores naphthalimide and rhodamine (Nph-A and Rh-T) were designed and synthesized. The two NPAs exhibit distinctive assembly behaviours with spherical (Rh-T) and fibrous (Nph-A) morphologies, and mixing Nph-A with Rh-T leads to a densely crosslinked colloidal network (Nph-A/Rh-T) via mutually promoted supramolecular polymerization via nucleation-growth assembly. Because of the RGD-rich sequences in the crosslinked network, further research on in situ targeted cancer cell (MDA-MB-231) encapsulation via RGD-integrin recognition was performed, and the modulation of cell behaviours (e.g., cell viability and migration) was demonstrated using both confocal laser scanning microscopy (CLSM) imaging and a scratch wound healing assay.

6.
ACS Appl Mater Interfaces ; 12(30): 33564-33574, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32633941

RESUMO

Because of the lack of specific targets, the highly aggressive triple negative breast cancer (TNBC) is unable to benefit from endocrine therapy or conventional targeting therapy. Even worse, current diagnostic and therapeutic approaches have limited value for TNBC. Therefore, developing TNBC-specific theranostic probes for accurate diagnosis and further selective therapy will build a powerful toolbox for TNBC management. In this contribution, we developed a sequential strategy to enhance the specificity of TNBC theranostics. In this theranostic system, a versatile nanoprobe (Pep-SQ@USPIO) was integrated legitimately for the fibronectin-targeting MR imaging and CTSB-activatable fluorescence imaging, followed with enhanced photodynamic therapy (PDT) of TNBC. First, the fibronectin overexpressed in the extracellular matrix (ECM) of TNBC was used as a biomarker for targeting theranostics using the Cys-Arg-Glu-Lys-Ala (CREKA) peptide. For another, the fluorescence and PDT capacity of self-developed squaraine photosensitizer (SQ) were prequenched by ultrasmall superparamagnetic iron oxide (USPIO), an MR imaging contrast agent. Once the linker, Gly-Phe-Leu-Gly (GFLG) peptide, was selectively cleaved by TNBC-derived CTSB, the liberated SQ photosensitizer allowed light-up fluorescence imaging and enhanced PDT of TNBC. Remarkably, this research demonstrates that tumor-ECM-targeting and endogenous enzyme-activated nanoprobes open a new avenue for TNBC theranostics.


Assuntos
Catepsina B/metabolismo , Fibronectinas/metabolismo , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/química , Ciclobutanos/química , Feminino , Compostos Férricos/química , Fibronectinas/genética , Humanos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Camundongos , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Imagem Óptica , Fenóis/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
7.
Chem Sci ; 11(2): 419-428, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-32190262

RESUMO

Semiconducting polymer (SP)-based afterglow luminogens are showing increasing potential for in vivo imaging because of their long-life luminescence and the associated benefits (e.g., zero-autofluorescence background and high signal-to-noise ratio). However, such organic afterglow luminescence agents are still rare and their application is usually limited by their relatively low afterglow intensity and short afterglow duration. Herein, we report an aggregation-induced emission (AIE) dye-powered SP afterglow luminogen by leveraging on the unique characteristics of an AIE dye to circumvent the concentration-quenching effect, enhance afterglow intensity and prolong afterglow duration. The underlying working mechanism is investigated by a series of experiments and it is found that the AIE dye provides sufficient 1O2 to excite SPs and form massive amounts of high-energy intermediates, and then the SP intermediates emit photons that can activate the AIE dye to generate 1O2 and simultaneously trigger the energy transfer process between the SPs and AIE dye, resulting in a deep-red emission. It is this closed-loop of "photon-1O2-SP intermediates-photon" that provides the afterglow emission even after the cessation of the excitation light. The as-prepared luminogen shows good performance in in vivo tumour imaging. This study demonstrates the advantages of AIE-facilitated afterglow luminescence and discloses its mechanism, and hopefully it could inspire the development of other innovative designs for cancer theranostics.

8.
ACS Appl Mater Interfaces ; 12(4): 4276-4284, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31896256

RESUMO

Various squaraine dyes have been developed for biological imaging. Nevertheless, squaraine dyes with emission in the second window (NIR-II, 1000-1700 nm) have few reports largely due to the short of a simple and universal design strategy. In this contribution, molecular engineering strategy is explored to develop squaraine dyes with NIR-II emission. First, NIR-I squaraine dye SQ2 is constructed by the ethyl-grafted 1,8-naphtholactam as donor units and square acid as acceptor unit in a donor-acceptor-donor (D-A-D) structure. To red-shift the fluorescence emission into NIR-II window, malonitrile, as a forceful electron-withdrawing group, is introduced to strengthen square acid acceptor. As a result, the fluorescence spectrum of acceptor-engineered squaraine dye SQ1 exhibits a significant red-shift into NIR-II window. To translate NIR-II fluorophores SQ1 into effective theranostic agents, fibronectin-targeting SQ1 nanoprobe was constructed and showed excellent NIR-II imaging performance in angiography and tumor imaging, including lung metastatic foci in deep tissue. Furthermore, SQ1 nanoprobe can be used for photoacoustic imaging and photothermal ablation of tumors. This research demonstrates that the donor-acceptor engineering strategy is feasible and effective to develop NIR-II squaraine dyes.


Assuntos
Neoplasias da Mama , Ciclobutanos , Hipertermia Induzida , Nanopartículas , Fenóis , Técnicas Fotoacústicas , Fototerapia , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Ciclobutanos/química , Ciclobutanos/farmacologia , Humanos , Células MCF-7 , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Fenóis/química , Fenóis/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Nanobiotechnology ; 17(1): 105, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604441

RESUMO

PURPOSE: To develop a novel fluorine-18 (18F)-labeled arginine-glycine-aspartic acid (RGD)-coupled ultra-small iron oxide nanoparticle (USPIO) (hereafter, referred to as 18F-RGD@USPIO) and conduct an in-depth investigation to monitor the anti-angiogenic therapeutic effects by using a novel dual-modality PET/MRI probe. METHODS: The RGD peptide and 18F were coupled onto USPIO by click chemistry. In vitro experiments including determination of stability, cytotoxicity, cell binding of the obtained 18F-RGD@USPIO were carried out, and the targeting kinetics and bio-distribution were tested on an MDA-MB-231 tumor model. A total of 20 (n = 10 per group) MDA-MB-231 xenograft-bearing mice were treated with bevacizumab or placebo (intraperitoneal injections of bevacizumab or a volume-equivalent placebo solution at the dose of 5 mg/kg for consecutive 7 days, respectively), and underwent PET/CT and MRI examinations with 18F-RGD@USPIO before and after treatment. Imaging findings were validated by histological analysis with regard to ß3-integrin expression (CD61 expression), microvascular density (CD31 expression), and proliferation (Ki-67 expression). RESULTS: Excellent stability, low toxicity, and good specificity to endothelial of 18F-RGD@USPIO were confirmed. The best time point for MRI scan was 6 h post-injection. No intergroup differences were observed in tumor volume development between baseline and day 7. However, 18F-RGD@USPIO binding was significantly reduced after bevacizumab treatment compared with placebo, both on MRI (P < 0.001) and PET/CT (P = 0.002). Significantly lower microvascular density, tumor cell proliferation, and integrin ß3 expression were noted in the bevacizumab therapy group than the placebo group, which were consistent with the imaging results. CONCLUSION: PET/MRI with the dual-modality nanoprobe, 18F-RGD@USPIO, can be implemented as a noninvasive approach to monitor the therapeutic effects of anti-angiogenesis in breast cancer model in vivo.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Dextranos/química , Radioisótopos de Flúor/química , Nanopartículas de Magnetita/química , Oligopeptídeos/química , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tomografia por Emissão de Pósitrons
10.
Nanoscale ; 11(13): 6307-6314, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30882834

RESUMO

Tumor-derived alkaline phosphatase (ALP) is over-expressed in metastatic prostate cancer. The development of selective probes for ALP detection is therefore critical for early diagnosis and therapy of metastatic prostate cancer. Herein, we develop a mitochondria-targeted near-infrared activatable fluorescent/photoacoustic (NIR FL/PA) probe for the selective detection of prostate cancer-derived ALP and aggregation-enhanced photothermal therapy. Upon dephosphorylation, the probes are activated and they provide a red-shifted strong absorption and emission in the NIR window and thus enable NIR FL and PA imaging of ALP activity in tumor tissues. Particularly, the activated probes self-assemble in situ into a supramolecular network structure which induces cell apoptosis and significantly enhances the photothermal therapy efficacy.


Assuntos
Fosfatase Alcalina/metabolismo , Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Fosfatase Alcalina/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Inibidores Enzimáticos/farmacologia , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/uso terapêutico , Humanos , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência , Técnicas Fotoacústicas , Fototerapia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Espectroscopia de Luz Próxima ao Infravermelho , Distribuição Tecidual
11.
Chem Sci ; 10(2): 398-405, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30746088

RESUMO

Development of fluorescent probes for on-site sensing and long-term tracking of specific biomarkers is particularly desirable for the early detection of diseases. However, available small-molecule probes tend to facilely diffuse across the cell membrane or remain at the activation site but always suffer from the aggregation-caused quenching (ACQ) effect. Here we report an enzyme-activatable aggregation-induced emission (AIE) probe QM-ßgal, which is composed of a hydrophilic ß-galactosidase (ß-gal)-triggered galactose moiety and a hydrophobic AIE-active fluorophore QM-OH. The probe is virtually non-emissive in aqueous media, but when activated by ß-gal, specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM-OH, and then highly fluorescent nanoaggregates are in situ generated as a result of the AIE process, allowing for on-site sensing of endogenous ß-gal activity in living cells. Notably, taking advantage of the improved intracellular retention of nanoaggregates, we further exemplify QM-ßgal for long-term (∼12 h) visualization of ß-gal-overexpressing ovarian cancer cells with high fidelity, which is essential for biomedicine and diagnostics. Thus, this enzyme-activatable AIE probe not only is a potent tool for elucidating the roles of ß-gal in biological systems, but also offers an enzyme-regulated liberation strategy to exploit multifunctional probes for preclinical applications.

12.
ACS Nano ; 12(12): 12169-12180, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30418734

RESUMO

Protein-assisted biomimetic synthesis has been an emerging offshoot of nanofabrication in recent years owing to its features of green chemistry, facile process, and ease of multi-integration. As a result, many proteins have been used for biomimetic synthesis of varying kinds of nanostructures. Although the efforts on exploring new proteins and investigating their roles in biomimetic chemistry are increasing, the most essential intrinsic properties of proteins are largely neglected. Herein we report a frequently used enzyme (horseradish peroxidase, HRP) to demonstrate the possibility of enzymatic activity retaining after accomplishing the roles in biomimetic synthesis of ultrasmall gadolinium (Gd) nanodots and stowing its substrate 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS), denoted as Gd@HRPABTS. It was found that ca. 70% of the enzymatic activity of HRP was preserved. The associated changes of protein structure with chemical treatments were studied by spectroscopic analysis. Leveraging on the highly retained catalytic activity, Gd@HRPABTS exerts strong catalytic oxidation of peroxidase substrate ABTS into photoactive counterparts in the presence of intrinsic H2O2 inside the tumor, therefore enabling tumor-selective catalytic photoacoustic (PA) imaging and photothermal therapy (PTT). In addition, the MR moiety of Gd@HRPABTS provides guidance for PTT and further diagrams that Gd@HRPABTS is clearable from the body via kidneys. Preliminary toxicity studies show no observed adverse effects by administration of them. This study demonstrates beyond the well-known roles in biomimetic chemistry that HRP can also preserve its enzymatic activity for tumor catalytic theranostics.


Assuntos
Antineoplásicos/farmacologia , Materiais Biomiméticos/farmacologia , Neoplasias da Mama/terapia , Peroxidase do Rábano Silvestre/metabolismo , Fototerapia , Nanomedicina Teranóstica , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Gadolínio/administração & dosagem , Gadolínio/química , Gadolínio/farmacologia , Peroxidase do Rábano Silvestre/administração & dosagem , Peroxidase do Rábano Silvestre/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/terapia , Camundongos , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Técnicas Fotoacústicas
13.
Chem Commun (Camb) ; 54(70): 9841-9844, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30110025

RESUMO

A peptide-modified gold nanoparticle was developed for tumour-targeted therapy. Triggered by alkaline phosphatase, the CREKA-YPFFK(Nph) peptide can self-assemble and further result in accumulation of gold nanoparticles in tumour cells. The large-sized gold nanoparticle aggregates cannot escape from the tumour tissue, therefore realizing the goal of tumour-specific targeting, enhanced retention and photothermal effects.


Assuntos
Antineoplásicos/uso terapêutico , Ouro/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Fosfatase Alcalina/metabolismo , Sequência de Aminoácidos , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Humanos , Luz , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Camundongos Endogâmicos BALB C , Oligopeptídeos/síntese química , Oligopeptídeos/metabolismo , Oligopeptídeos/efeitos da radiação , Oligopeptídeos/toxicidade , Tamanho da Partícula , Fototerapia/métodos , Temperatura
15.
ACS Appl Mater Interfaces ; 8(9): 5847-56, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26910257

RESUMO

Lysophosphatidic acid (LPA, cutoff values ≥ 1.5 µM) is an effective biomarker for early stage ovarian cancer. The development of selective probes for LPA detection is therefore critical for early clinical diagnosis. Although current methods have been developed for the detection of LPA in solution, they cannot be used for tracking LPA in vivo. Here, we report a near-infrared (NIR) fluorescent probe that can selectively respond to LPA based on polarity-sensitive emission at a very low detection limit of 0.5 µM in situ. This probe exhibits a marked increase of fluorescence at 720 nm upon binding to LPA, allowing the direct visualization of LPA in vitro and in vivo without interference from other biomolecules. Moreover, the probe containing two arginine-glycine-aspartic acid units can be efficiently taken up by cancer cells based on an αvß3 integrin receptor targeting mechanism. It also exhibits excellent biocompatibility and high pH stability in live cells and in vivo. Confocal laser scanning microscopy and flow cytometric imaging of SKOV-3 cells have confirmed that our probe can be used to image LPA in live cells. In particular, its NIR turn-on fluorescence can be used to effectively monitor LPA imaging in a SKOV-3 tumor-bearing mouse model. Our probe may pave the way for the detection of cancer-related biomarkers and even for early stage cancer diagnosis.


Assuntos
Biomarcadores Tumorais/análise , Corantes Fluorescentes/química , Lisofosfolipídeos/análise , Neoplasias Ovarianas/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Biomarcadores Tumorais/química , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Corantes Fluorescentes/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Lisofosfolipídeos/química , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Oligopeptídeos/química , Neoplasias Ovarianas/patologia , Transplante Heterólogo
16.
Nanoscale ; 6(24): 14772-83, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25355048

RESUMO

Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 µg mL(-1) (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for designing functional liposomes to act as anticancer agents.


Assuntos
Magaininas/administração & dosagem , Nanocápsulas/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Polímeros/química , Poli-Inos/química , Proteínas de Xenopus/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Difusão , Desenho de Fármacos , Corantes Fluorescentes/química , Magaininas/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Microscopia de Fluorescência/métodos , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Polímero Poliacetilênico , Resultado do Tratamento , Proteínas de Xenopus/química
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