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1.
Adv Mater ; : e2102950, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617645

RESUMO

Lanthanide-based NIR-IIb nanoprobes are ideal for in vivo imaging. However, existing NIR-IIb nanoprobes often suffer from low tumor-targeting specificity, limiting their widespread use. Here the application of bioorthogonal nanoprobes with high tumor-targeting specificity for in vivo NIR-IIb luminescence imaging and magnetic resonance imaging (MRI) is reported. These dual-modality nanoprobes can enhance NIR-IIb emission by 20-fold and MRI signal by twofold, compared with non-bioorthogonal nanoprobes in murine subcutaneous tumors. Moreover, these bioorthogonal probes enable orthotopic brain tumor imaging. Implementation of bio-orthogonal chemistry significantly reduces the nanoprobe dose and hence cytotoxicity, providing a paradigm for real-time in vivo visualization of tumors.

2.
ACS Nano ; 15(6): 10010-10024, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34060821

RESUMO

Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as pancreatic cancer. Herein, we aim to develop metabolizable dextran-indocyanine green (DN-ICG) nanoprobes in the second near-infrared window (NIR-II, 1 000-1 700 nm) for dynamic imaging of TAMs in pancreatic cancer. Compared to free ICG, the NIR-II fluorescence intensity of DN-ICG nanoprobes increased by 279% with significantly improved stability. We demonstrated that DN-ICG nanoprobes could specifically target TAMs through the interaction of dextran with specific ICAM-3-grabbing nonintegrin related 1 (SIGN-R1), which were highly expressed in TAMs. Subsequently, DN-ICG nanoprobes gradually metabolized in the liver yet remained in pancreatic tumor stroma in mouse models, achieving a high signal-to-background ratio (SBR = 7) in deep tissue (∼0.5 cm) NIR-II imaging of TAMs. Moreover, DN-ICG nanoprobes could detect dynamic changes of TAMs induced by low-dose radiotherapy and zoledronic acid. Therefore, the highly biocompatible and biodegradable DN-ICG nanoprobes harbor great potential for precision therapy in pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Macrófagos Associados a Tumor , Animais , Verde de Indocianina , Camundongos , Imagem Óptica , Neoplasias Pancreáticas/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho
3.
Small ; 17(43): e2101397, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34159726

RESUMO

In this study, to visually acquire all-round structural and functional information of lung cancer while performing synergistic photothermal therapy (PTT) and tumor-targeting immunotherapy, a theranostic nanoplatform that introduced upconversion nanoparticles (UCNPs) and IR-1048 dye into the lipid-aptamer nanostructrure (UCILA) is constructed. Interestingly, the IR-1048 dye grafted into the lipid bilayer can serve as the theranostic agent for photoacoustic imaging, optical coherence tomography angiography, photothermal imaging, and PTT in the second near infrared (NIR-II) window. In addition, loaded in the inner part of UCILA, UCNPs possess the superior luminescence property and high X-ray attenuation coefficient, which can act as contrast agents for computed tomography (CT) and thermo-sensitive up-conversion luminescence (UCL) imaging, enabling real-time tracking of metabolic activity of tumor and temperature-feedback PTT. Furthermore, under the complementary guidance of penta-modal imaging and an accurate monitoring of in situ temperature change during PTT, UCILA exhibits its excellent capability for ablating the lung tumor with minimal side effects. Meanwhile, synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT. Therefore, the UCILA nanoplatform is demonstrated as a multifunctional theranostic agent for both penta-modal imaging and temperature-feedback PTT while conducting targeting immunotherapy of lung cancer.


Assuntos
Hipertermia Induzida , Neoplasias Pulmonares , Nanopartículas , Rubiaceae , Linhagem Celular Tumoral , Retroalimentação , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Fototerapia , Terapia Fototérmica , Temperatura , Nanomedicina Teranóstica
4.
J Mater Chem B ; 9(13): 3005-3014, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33704309

RESUMO

Photoacoustic (PA) imaging with functional nanoprobes in the second near-infrared region (NIR-II, 1000-1700 nm) has aroused much interest due to its deep tissue penetration and high maximum laser permissible exposure. However, most NIR-II PA imaging is performed using the two-dimensional (2D) imaging modality, which impedes the comprehension of the in vivo biodistribution, angiography and molecular-targeted performance of NIR-II nanoprobes (NPs). Herein, we report the systematic monitoring of biomineralized copper sulfide (CuS) NPs, typical NIR-II NPs, in mouse models by employing NIR-II three-dimensional (3D) PA imaging. The advanced imaging modality provides dynamic information about the 3D biodistribution and metabolic pathway of CuS NPs. We also achieved contrast-enhanced 3D PA imaging of abdominal and cerebral vessels at a high signal-to-background ratio. Moreover, the tumor-targeted CuS NPs conjugated with the bombesin peptide endowed NIR-II 3D PA with superior performance in imaging orthotopic tumors both deep in the prostate and in the brain beneath the intact scalp and skull. Our results highlight the potential of NIR-II 3D PA imaging for the evaluation of the in vivo behavior of NPs, thus providing a promising strategy for screening NPs in clinical translational studies.


Assuntos
Cobre/química , Corantes Fluorescentes/química , Nanopartículas/química , Técnicas Fotoacústicas , Neoplasias da Próstata/diagnóstico por imagem , Sulfetos/química , Animais , Células HEK293 , Humanos , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/diagnóstico por imagem , Tamanho da Partícula , Células Tumorais Cultivadas
5.
ACS Appl Mater Interfaces ; 12(50): 55624-55637, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33269904

RESUMO

Cancer phototheranostics in the second near-infrared window (NIR-II, 1000-1700 nm) has recently attracted much attention owing to its high efficacy and good safety compared with that in the first near-infrared window (NIR-I, 650-950 nm). However, the lack of theranostic nanoagents with active-targeting features limits its further application in cancer precision therapies. Herein, we constructed platelet-camouflaged nanoprobes with active-targeting characteristics for NIR-II cancer phototheranostics. The as-prepared biomimetic nanoprobes can not only escape phagocytosis by macrophages but also specifically bind to CD44 on the surface of most cancer cells. We evaluated the active-targeting performance of biomimetic nanoprobes in pancreatic cancer, breast cancer, and glioma mouse models and achieved NIR-II photoacoustic imaging with a high signal-to-background ratio and photothermal treatment with excellent tumor growth inhibition. Our results show the great potential of platelet-camouflaged nanoprobes with NIR-II active-targeting features for cancer precision diagnosis and efficient therapies.


Assuntos
Raios Infravermelhos , Lipossomos/química , Proteínas de Membrana/química , Nanopartículas/química , Animais , Plaquetas/citologia , Plaquetas/metabolismo , Linhagem Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Nus , Nanopartículas/uso terapêutico , Nanopartículas/toxicidade , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fagocitose , Técnicas Fotoacústicas , Fototerapia , Transplante Homólogo
6.
Biomed Opt Express ; 11(11): 6721-6731, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33282520

RESUMO

Intravascular photoacoustic (IVPA) imaging technology enables the visualization of pathological characteristics (such as inflammation activities, lipid deposition) of the artery wall. Blood flushing is a necessary step in improving the imaging quality in in vivo IVPA imaging. But the limited imaging speed of the systems stretches their flushing time, which is an important obstacle of their clinical translations. In this paper, we report an improvement in IVPA/IVUS imaging speed to 100 frames per second. The high-speed imaging is demonstrated in rabbit in vivo, visualizing the nanoparticles accumulated on abdominal aorta wall at the wavelength of 1064 nm, in real time display. Blood flushing in vivo improves the IVPA signal-noise-ratio by around 3.5 dB. This study offers a stable, efficient and easy-to-use tool for instantaneous disease visualization and disease diagnosis in research and forwards IVPA/IVUS imaging technology towards clinical translations.

7.
Research (Wash D C) ; 2020: 4074593, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33063015

RESUMO

Fluorescence probes with aggregation-induced emission (AIE) characteristics are of great importance in biomedical imaging with superior spatial and temporal resolution. However, the lack of toxicity studies and deep tissue imaging in nonhuman primates hinders their clinical translation. Here, we report the blood chemistry and histological analysis in nonhuman primates treated with AIE probes over tenfold of an intravenous dose of clinically used indocyanine green (ICG) during a study period of 36 days to demonstrate AIE probes are nontoxic. Furthermore, through bright and nontoxic AIE probes and fluorescence imaging in the second window (NIR-II, 1,000-1,700 nm), we achieve an unprecedented 1.5-centimeter-deep vascular imaging in nonhuman primates, breaking the current limitation of millimeter-deep NIR-II fluorescence imaging. Our important findings, i.e., nontoxic features of AIE probes and centimeter-deep NIR-II vascular imaging in nonhuman primates, may facilitate successful translation of AIE probes in clinical trials.

8.
Mol Pharm ; 17(10): 3720-3729, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32633977

RESUMO

The limited tumor tissue penetration of many nanoparticles remains a formidable challenge to their therapeutic efficacy. Although several photonanomedicines have been applied to improve tumor penetration, the first near-infrared window mediated by the low optical tissue penetration depth severely limits their anticancer effectiveness. To achieve deep optical tissue and drug delivery penetration, a near-infrared second window (NIR-II)-excited and pH-responsive ultrasmall drug delivery nanoplatform was fabricated based on BSA-stabilized CuS nanoparticles (BSA@CuS NPs). The BSA@CuS NPs effectively encapsulated doxorubicin (DOX) via strong electrostatic interactions to form multifunctional nanoparticles (BSA@CuS@DOX NPs). The BSA@CuS@DOX NPs had an ultrasmall size, which allowed them to achieve deeper tumor penetration. They also displayed stronger NIR II absorbance-mediated deep optical tissue penetration than that of the NIR I window. Moreover, the multifunctional nanoplatform preferentially accumulated in tumor sites, induced tumor hyperthermia, and generated remarkably high ROS levels in tumor sites upon NIR-II laser (1064 nm) irradiation. More importantly, our strategy achieved excellent synergistic effects of chemotherapy and phototherapy (chemophototherapy) under the guidance of photothermal imaging. The developed nanoparticles also showed good biocompatibility and bioclearance properties. Therefore, our work demonstrated a facile strategy for fabricating a multifunctional nanoplatform that is a promising candidate for deep tumor penetration as an effective antitumor therapy.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/efeitos da radiação , Nanopartículas/efeitos da radiação , Neoplasias/tratamento farmacológico , Fototerapia/métodos , Animais , Linhagem Celular Tumoral/transplante , Sobrevivência Celular , Modelos Animais de Doenças , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos da radiação , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Lasers , Camundongos , Nanopartículas/química , Neoplasias/patologia , Fototerapia/instrumentação , Distribuição Tecidual
9.
Biomaterials ; 251: 120092, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32388165

RESUMO

Multidrug-resistant Staphylococcus aureus (MRSA) seriously endanger human health. The development of efficient methods to eliminate the infections and monitor the treatment process are of great significance. Near-infrared-II (NIR-II) photoacoustic (PA) imaging and photothermal therapy (PTT) are highly integrated theranostic platforms with superior performance including a low imaging background, increased tissue penetration depth, and high photothermal threshold. Herein, we report an activatable near-infrared II (NIR-II) phototheranostic strategy using miniature Au/Ag nanorods (NRs) for the photochemical synergistic therapy of MRSA infections and in situ monitoring of the treatment progress. Au/Ag NRs were efficiently activated by ferricyanide solution and allowed to continuously release free Ag+ to eliminate MRSA, triggering NIR-II photothermal and PA performance enhancement. The activated NIR-II photothermal effect in turn accelerated the release of free Ag+ from Au/Ag NRs for the synergistic elimination of gram-positive Staphylococcus aureus and promoted wound healing. No photothermal damages or free Ag+-induced side effects were observed in treated mice. After synergistic treatment, a 20-fold NIR-II PA signal increase with a maximum signal-to-noise measurement of 9.5 was observed between the implanted site and normal tissue, enabling sensitive monitoring of Ag+ release process. The prepared Au/Ag NRs were stable and biocompatible, showing great potential for activatable NIR-II phototheranostic application.

10.
Biomater Sci ; 8(3): 973-987, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31850404

RESUMO

Photodynamic therapy (PDT) and radiotherapy (RT) are oxygen-dependent treatment strategies for solid tumors in clinics. However, the hypoxic tumor microenvironment induced by uncontrolled cancer cell proliferation significantly reduces the therapeutic efficacy of these strategies. Here, we rationally constructed indocyanine green (ICG)-loaded ultrasmall gold nanoclusters (Au NCs-ICG) as theranostic nanozymes for modulating tumor hypoxia and augmenting cancer PDT and RT, respectively. The constructed Au NC-ICG nanozymes with an ultrasmall particle size (∼1 nm) exhibited favorable renal clearance performance, high substrate affinity (Km≈ 2 mM) and good catalase-like activity (Vmax≈ 4.55 × 10-3 mM s-1). In 4T1 tumor-bearing mouse models, high tumor accumulation of Au NC-ICG nanozymes was clearly visualized by near-infrared fluorescence, photoacoustic and computed tomography imaging, showing the potential for the monitoring and guidance of PDT and RT. In addition, the Au NCs-ICG nanozymes effectively decomposed intratumoral H2O2 into O2 for overcoming hypoxia and subsequently enhancing PDT and RT, respectively. Moreover, the inherent X-ray absorption capacity of Au NCs-ICG greatly deposited radiation energy within the tumor region and further improved cancer RT. The integration of multimodal imaging, tumor hypoxia regulation, and effective therapy into ultrasmall Au NCs-ICG nanozymes shows great potential for cancer theranostic applications.


Assuntos
Verde de Indocianina/administração & dosagem , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Linhagem Celular Tumoral , Feminino , Ouro/administração & dosagem , Ouro/química , Humanos , Verde de Indocianina/química , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Fotoquimioterapia , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/efeitos da radiação
11.
Theranostics ; 9(18): 5315-5331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410217

RESUMO

Background: Engineering a single organic-molecule-based nanoparticle integrating precise diagnosis and effective therapy is of great significance for cancer treatment and future clinical applications but remains a great challenge. The goal of this study is to explore small organic molecule-based nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided therapy. Methods: Heptacyclic B, O-chelated BODIPY structure (namely Boca-BODIPY) with strong near-infrared (NIR) absorption was designed as a theranostic agent through simply molecular engineering, in which heavy atoms and alkyl chains were introduced to promote its application for tumor theranostics. The Boca-BODIPY molecules are further encapsulated in reduced bovine serum albumin (BSA) through self-assembly. Results: The BSA-Boca-BODIPY exhibited excellent biocompatibility, extraordinary stability and high photothermal conversion efficiency up to 58.7%. The nanoparticles could dramatically enhance photoacoustic contrast of the tumor region, and the signal-to-noise ratio was increased about 14 times at 10 h post intravenous injection in 4T1 tumor-bearing mice. In addition, the nanoassemblies can efficiently convert laser energy (808 nm, 0.75 w cm-2, 5min) into hyperthermia for tumor ablation. Under the photoacoustic imaging-guided photothermal therapy (PTT), the 4T1 cancer cells were efficiently killed, no tumor recurrence and PTT-induced toxicity is observed. Conclusions: Molecular engineering is a promising way to design organic-molecule-based nanoparticles for cancer theranostics. Other organic-molecule-based nanoparticles which show great promise for imaging-guided cancer precision therapy can be engineered through this method.


Assuntos
Compostos de Boro/química , Hipertermia Induzida , Raios Infravermelhos , Nanopartículas/química , Neoplasias/terapia , Técnicas Fotoacústicas , Fototerapia , Nanomedicina Teranóstica , Animais , Compostos de Boro/síntese química , Morte Celular , Linhagem Celular Tumoral , Fluorescência , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Neoplasias/diagnóstico
12.
Chem Commun (Camb) ; 55(44): 6209-6212, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31073580

RESUMO

In this study, pH-sensitive loaded retinal/indocyanine green (ICG) micelles were developed to realize novel approaches for cellular senescence-photothermal synergistic therapy to treat cancer. The micelles could enable effective multi-modal imaging in vivo guided therapy and show anticancer activity in vitro and in vivo with satisfactory biosafety.


Assuntos
Senescência Celular , Concentração de Íons de Hidrogênio , Verde de Indocianina/metabolismo , Micelas , Imagem Multimodal , Fototerapia/métodos , Retinaldeído/metabolismo , Nanomedicina Teranóstica , Humanos , Neoplasias/patologia
13.
Angew Chem Int Ed Engl ; 58(9): 2744-2748, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30657623

RESUMO

Semiconducting polymer dots (Pdots) have recently attracted considerable attention because of their photocatalytic activity as well as tunable optical band gap. In this contribution, we describe the therapeutic application of Pdots through in situ photocatalytic hydrogen generation. Liposomes were employed as nanoreactors to confine the Pdot photocatalyst, reactants, intermediates, and by-products. Upon photon absorption by the Pdots, the catalytic cycle is initiated and repeated within the aqueous interior, while the H2 product diffuses across the lipid bilayer to counteract reactive oxygen species (ROS) overexpressed in diseased tissues. Ensemble and single-particle Förster resonance energy transfer microscopy confirmed the proposed nanoreactor model. We demonstrate that a liposomal nanoreactor containing Pdots and a sacrificial electron donor is a potential photocatalytic nanoreactor for in situ hydrogen therapy.


Assuntos
Hidrogênio/química , Polímeros/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Catálise , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Lipossomos/química , Lipossomos/farmacologia , Camundongos , Estrutura Molecular , Processos Fotoquímicos , Polímeros/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Semicondutores
14.
Biomater Sci ; 7(4): 1486-1492, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30672925

RESUMO

To date, photoacoustic imaging (PAI) and PAI-guided photothermal therapy (PTT) have been performed for noninvasive cancer diagnosis and precise ablation of tumors. To conduct concurrent PAI and PTT, it is essential to develop theranostic agents with strong optical absorption and high photothermal transfer efficiency. In this study, we have engineered theranostic agents with tunable absorptions based on conjugated polymer dots (Pdots) with different structures via the simple precipitation method. The as-synthesized Pdots exhibit strong absorption, high biocompatibility, and superior stability. In addition, the Pdots demonstrate that they can serve as contrast agents for multiscale PAI in vitro and in vivo. More importantly, a high photothermal conversion efficiency up to 40% is reached under irradiation with LED light, resulting in effective cancer treatment with extremely low light dose. Consequently, they show the potential as imaging-guided therapeutic agents for clinical cancer treatment and various biomedical applications.


Assuntos
Materiais Biocompatíveis/farmacologia , Neoplasias da Mama/tratamento farmacológico , Meios de Contraste/farmacologia , Fototerapia , Polímeros/farmacologia , Tiofenos/farmacologia , Engenharia Tecidual , Absorção Fisiológica/efeitos dos fármacos , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/síntese química , Meios de Contraste/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Técnicas Fotoacústicas , Polímeros/síntese química , Polímeros/química , Relação Estrutura-Atividade , Nanomedicina Teranóstica , Tiofenos/química
15.
J Biophotonics ; 12(3): e201800237, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30414259

RESUMO

In this study, CuS nanoparticles with optical absorption covering both near-infrared I (NIR-I) and NIR-II biological windows were prepared and served as the contrast agents for multispectral photoacoustic imaging. The physiological parameters including concentrations of deoxyhemoglobin and oxyhemoglobin as well as the water content in the tumor location were quantified based on the multispectral photoacoustic reconstruction method. More importantly, the concentration of CuS nanoparticles/drugs accumulated in the tumor was also recovered after intravenously injection, which are essential for image-guided cancer theranostics. In addition, phantom and in vivo experimental tests were performed to inspect and compare the imaging depth and signal-to-noise ratio (SNR) between the two NIR biological windows. Interestingly, we discovered that a higher SNR was obtained in the NIR-II window than that in the NIR-I window. Meanwhile, the multispectral imaging results also demonstrated that the imaging contrast and penetration depth in the NIR-II window were also significantly improved as compared to those from the NIR-I window.


Assuntos
Cobre/química , Raios Infravermelhos , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Tomografia/métodos , Linhagem Celular Tumoral , Meios de Contraste/química , Células HEK293 , Humanos , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Razão Sinal-Ruído
16.
Nanoscale ; 10(42): 19742-19748, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30328874

RESUMO

Engineering conjugated polymer nanoparticles (CPNs) with an easily-modified surface is essential to construct multifunctional nanoprobes as contrast agents for dual-modal photoacoustic (PA) and fluorescence imaging, which can take advantages of the complementary information from a single modality. In this study, an abundant protein with plenty of functional groups was introduced for the first time to produce easily-modified CPNs, leading to a robust nanoplatform to engineer PA-based multifunctional nanoprobes due to their strong optical absorption in the near-infrared region. Meanwhile, the bovine serum albumin (BSA)-modified CPNs were further engineered by introducing gold clusters in situ, which can serve as fluorescent nanoprobes for dual-modal molecular imaging. In particular, the developed nanoplatform exhibited superior stability and excellent biocompatibility, making it an ideal candidate for various cancer-theranostics applications. More importantly, our imaging results demonstrated that the BSA-modified CPNs were excellent candidates to design PA-based contrast agents for multimodal imaging using the function of the protein. In addition, other functional blocks can also be added to the nanoplatform based on its easily-modified surface, making it a general method for the construction of multifunctional nanoprobes for disease theranostics.


Assuntos
Nanopartículas/química , Imagem Óptica , Técnicas Fotoacústicas , Polímeros/química , Animais , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/química , Ouro/química , Células HEK293 , Humanos , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Neoplasias/diagnóstico por imagem , Soroalbumina Bovina/química , Distribuição Tecidual , Transplante Heterólogo
17.
Nanoscale ; 10(36): 17283-17292, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30198041

RESUMO

Photodynamic therapy (PDT) is an alternative strategy for treating pancreatic cancer (PC) in clinics. However, the therapeutic efficacy is generally suppressed by inadequate oxygen supply in the hypoxic tumor microenvironment. Herein, hierarchical zeolite nanocarriers with hydrophilic mesoporous nanostructures and excellent biodegradability are synthesized via a one-pot wet chemical method. By co-loading with catalase and methylene blue (MB), a new type of oxygen self-sufficient PDT platform, a zeolite-catalase-MB nanocapsule (ZCM nanocapsule), is developed. After precision implantation of the ZCM nanocapsule into the tumor area under the real-time ultrasound (US) imaging guidance, the nanocapsule with 90% relative activity of equivalent free catalase enzyme efficiently modulates the tumor hypoxia and enhances the intratumoral US contrast by sustained decomposition of endogenous H2O2 and in situ production of O2 gas bubbles. Meanwhile, the MB loading in hierarchical zeolite matrices prevents the rapid leaching of the photosensitizer in tumor tissue, achieving a good sustained photosensitizer release effect. Based on the synchronous mechanisms, upon near-infrared laser irradiation, the local PC cells are completely killed, and no therapy-induced toxicity and recurrence are observed. This highly biocompatible and biodegradable hierarchical nanozeolite would further facilitate the development of catalase-based catalytic nanomedicine for enhancing chemotherapy, radiotherapy and combination therapy.


Assuntos
Catalase/administração & dosagem , Nanocápsulas , Oxigênio , Neoplasias Pancreáticas/tratamento farmacológico , Fotoquimioterapia , Zeolitas , Animais , Linhagem Celular Tumoral , Células HEK293 , Humanos , Peróxido de Hidrogênio , Hipóxia , Azul de Metileno/administração & dosagem , Camundongos Nus , Neoplasias Pancreáticas/diagnóstico por imagem , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Quant Imaging Med Surg ; 8(3): 326-332, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29774185

RESUMO

Background: Construction of nanoprobes for dual-modal fluorescence/photoacoustic imaging (PAI) is of great importance for the detection of disease pathology and the development of innovative therapeutics. Previously ultra-small gold clusters were designed and used as contrast agents for fluorescence imaging (FLI). However, it is not clear whether they can also serve as promising probes for PAI. In this study, protein-modified ultra-small gold clusters are produced and examined quantitatively as enhanced contrast agents for dual-modal in vivo fluorescence and PAI. Methods: To construct the dual-modal ultra-small gold clusters, HAuCl4·4H2O aqueous solution was first mixed with the protein solution. NaOH was further introduced to the solution under vigorous stirring. The as-designed dual-modal nanoprobe was formed after stirring for 2 h at 65 °C. And then the solution was purified by gel column for further application. Zebrafish, cultivated in the solution containing gold clusters, was used in this study to demonstrate the dual-modal imaging ability of the nanoprobe by using our home-made optical-resolution photoacoustic microscopy and commercial fluorescence microscopy systems. Results: The gold nanoclusters were synthesized with diameters of about 3 nm, which showed the broad absorption with a characteristic peak centered at 520 nm. A strong near-infrared emission ranging from 600 to 750 nm was also observed for the gold clusters. In addition, the cell viability was more than 90% even at a high concentration of the nanoprobes. The zebrafish cultivated with the gold clusters exhibited dramatically enhanced fluorescence and photoacoustic signal intensities. Conclusions: Quantitative analysis results demonstrated that BSA-modified gold clusters were excellent contrast agents for in vivo dual-modal fluorescence/PAI. Due to their ultra-small size and superior biocompatibility, they can be applied to the detection and treatment of various diseases with enhanced sensitivity.

19.
ACS Appl Mater Interfaces ; 10(8): 7012-7021, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29400051

RESUMO

Theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, most photothermal agents are limited by their instability and low photothermal conversion efficiency. In this study, we report new conjugated polymer dots (Pdots) as multifunctional agents for photoacoustic (PA) imaging-guided PTT. The novel 4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene-6,6'-dibromo-N,N'-(2-ethylhexyl)isoindigo (BDT-IID) Pdots are readily fabricated though nanoreprecipitation and can absorb strongly in the 650-700 nm region. Furthermore, the BDT-IID Pdots possess a stable nanostructure and an extremely low biotoxicity. In particular, its photothermal conversion efficiency can be up to 45%. More importantly, our in vivo results exhibit that the BDT-IID Pdots are able to offer concurrently enhanced PA contrast and sufficient photothermal effect. Consequently, the BDT-IID Pdots can be exploited as a unique theranostic nanoplatform for PA imaging-guided PTT of tumors, holding great promise for their clinical translational development.


Assuntos
Técnicas Fotoacústicas , Nanopartículas , Fototerapia , Polímeros , Nanomedicina Teranóstica
20.
Theranostics ; 8(3): 663-675, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29344297

RESUMO

Optical nanomaterials with intense absorption in near-infrared (NIR) region hold great promise for biomedical applications such as photothermal therapy (PTT) and photoacoustic imaging (PAI). In this work, we report mesoporous carbon nanospheres (Meso-CNs) with broadband and intense absorption in the UV-Vis-NIR region (300-1400 nm) and explore their potential as a multifunctional platform for photoacoustic imaging and chemo-photothermal therapy. Methods: Meso-CNs were prepared by a "silica-assisted" synthesis strategy and characterized by transmission electron microscope and optical spectroscopy. We investigated the photothermal conversion and photoacoustic imaging of Meso-CNs in comparison with single-walled carbon nanotubes (SWCNTs), graphene and gold nanorods (GNRs). In vitro cellular assays and in vivo chemo-photothermal combination therapy were performed. Results: The absorption coefficients of Meso-CNs are 1.5-2 times higher than those of SWCNTs and graphene and are comparable to those of GNRs in both the first and the second near-infrared optical windows (NIR-I and NIR-II) of tissues. When exposed to an NIR laser, the photothermal and photoacoustic signal generation of Meso-CNs are also stronger than those of SWCNTs, graphene, and GNRs. DOX was loaded into Meso-CNs with a high efficiency (35 wt%) owing to the unique mesoporous structure. Particularly, the drug release from Meso-CNs is sensitive to both pH and NIR light stimulation. In vivo chemo-photothermal combination therapy demonstrates a remarkable inhibition effect on tumor growth under NIR laser treatment. Conclusions: We have developed Meso-CNs for photothermal conversion and photoacoustic imaging. The porous structure also serves as a drug carrier and the drug release can be controlled by pH and external light. The high drug loading capacity, superior photothermal and photoacoustic generation, together with the apparent chemo-photothermal therapeutic effect, make Meso-CNs a promising platform for cancer theranostics.


Assuntos
Portadores de Fármacos/química , Nanosferas/química , Neoplasias Experimentais/tratamento farmacológico , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Carbono/química , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos ICR , Neoplasias Experimentais/diagnóstico por imagem
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