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An ultrahigh-speed, wide-field OCT system for the imaging of anterior, posterior, and ocular biometers is crucial for obtaining comprehensive ocular parameters and quantifying ocular pathology size. Here, we demonstrate a multi-parametric ophthalmic OCT system with a speed of up to 1 MHz for wide-field imaging of the retina and 50 kHz for anterior chamber and ocular biometric measurement. A spectrum correction algorithm is proposed to ensure the accurate pairing of adjacent A-lines and elevate the A-scan speed from 500 kHz to 1 MHz for retinal imaging. A registration method employing position feedback signals was introduced, reducing pixel offsets between forward and reverse galvanometer scanning by 2.3 times. Experimental validation on glass sheets and the human eye confirms feasibility and efficacy. Meanwhile, we propose a revised formula to determine the "true" fundus size using all-axial length parameters from different fields of view. The efficient algorithms and compact design enhance system compatibility with clinical requirements, showing promise for widespread commercialization.
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Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-ß signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.
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Immunotherapy has achieved notable success in tumor treatment, but it is restricted to a small number of patients due to multiple immunosuppressive pathways in the tumor microenvironment. Here, we present a step-by-step protocol to prepare functional cellular nanovesicles from HEK293-FT cells displaying PD1 and TRAIL. TRAIL specifically induces immunogenic cancer cell death to initiate an immune response, and ectogenic PD1 blocks the PD1/PDL1 checkpoint signal to reactivate anergic tumor-specific CD8+ T cells. For complete details on the use and execution of this protocol, please refer to Wu et al. (2020).
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Linfócitos T CD8-Positivos/imunologia , Imunoterapia , Nanoestruturas/uso terapêutico , Neoplasias , Receptor de Morte Celular Programada 1 , Ligante Indutor de Apoptose Relacionado a TNF , Células HEK293 , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/uso terapêutico , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Ligante Indutor de Apoptose Relacionado a TNF/uso terapêuticoRESUMO
Recently, photothermal therapy (PTT) in the second near-infrared (NIR-II) biowindow has emerged as a promising treatment modality; however, its therapeutic outcomes are still limited by heterogeneous heat distribution and insufficient control of metastatic lesions. Tremendous efforts have been made to overcome the PTT's shortcomings by combining PTT with immunotherapy, but unfortunately current strategies still suffer from low response rates, primary/acquired resistance or severe immune-related adverse events. Herein, a novel photothermal agent and gene co-delivery nanoparticle (CSP), with CuS inside the SiO2 pore channels and PDMAEMA polycation on the outside of SiO2 surface, is explored for tumor localized NIR-II PTT and in situ immunotherapy through local generation of IL-12 cytokine. The resulting CSP integrated with the plasmid encoding IL-12 gene (CSP@IL-12) exhibited good gene transfection efficiency, outstanding NIR-II PTT effect and excellent therapeutic outcomes both in vitro and in vivo. Meanwhile, such an in situ joint therapy modality could significantly induce systemic immune responses including promoting DC maturation, CD8+ T cell proliferation and infiltration to efficiently eliminate possible metastatic lesions through abscopal effects. Hence, this creative combinational strategy of NIR-II PTT and IL-12 cytokine therapy might provide a more efficient, controllable and safer alternative strategy for future photo-immunotherapy.
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Hipertermia Induzida , Neoplasias , Citocinas , Humanos , Imunoterapia , Interleucina-12/genética , Neoplasias/terapia , Fototerapia , Dióxido de SilícioRESUMO
Immune cold tumor characterized by low immunogenicity, insufficient and exhausted tumor-infiltrating lymphocytes, and immunosuppressive microenvironment is the main bottleneck responsible for low patient response rate of immune checkpoint blockade. Here, we developed biosynthetic functional vesicles (BFVs) to convert immune cold into hot through overcoming hypoxia, inducing immunogenic cell death, and immune checkpoint inhibition. The BFVs present PD1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the surface, whereas load catalase into their inner core. The TRAIL can specifically induce immunogenic death of cancer cells to initiate immune response, which is further synergistically strengthened by blocking PD1/PDL1 checkpoint signal through ectogenic PD1 proteins on BFVs. The catalase can produce O2 to overcome tumor hypoxia, in turn to increase infiltration of effector T cells while deplete immunosuppressive cells in tumor. The BFVs elicit robust and systematic antitumor immunity, as demonstrated by significant regression of tumor growth, prevention of abscopal tumors, and excellent inhibition of lung metastasis.
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The development of nanotheranostic agents integrating diagnosis and therapy has gained tremendous attention in the past few decades, but many of them are inherently hydrophobic and need complicated phase-transfer and tedious surface modifications. This work proposed a facile method of transferring hydrophobic Fe3O4@Cu2-xS nanoparticles from oil to water by using red blood cell membrane to create theranostic nanobeads for T2-weighted MRI and second near-infrared photothermal ablation. The obtained nanoplatform, namely SCS@RBCM, showed a core-shell structure with the inner core densely packed with Fe3O4@Cu2-xS nanoclusters and the surface coated with a layer of RBCM. SCS@RBCM displayed a stable nanostructure, high NIR II light absorption and photothermal conversion ability, T2-weighted MR imaging and magnetic field targeting ability. Meanwhile, the RBCM cloaking endowed SCS with reduced elimination by macrophages. With the navigation of an external magnetic field (MF), the tumor accumulation of SCS@RBCM was dramatically increased, thus achieving good performance of MR imaging and antitumor efficacy through the PTT effect under NIR II irradiation. Therefore, our strategy presents a new and desirable paradigm in the phase-transfer of hydrophobic nanotheranostics for optimizing their biomedical performance.
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Membrana Celular/química , Eritrócitos/química , Imageamento por Ressonância Magnética , Nanopartículas/química , Fototerapia , Nanomedicina Teranóstica , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cobre/química , Compostos Férricos/química , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Hipertermia Induzida , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Transição de Fase , Enxofre/química , Propriedades de SuperfícieRESUMO
Herein, a bovine serum albumin-stabilized gold clusters-MnO2 nanocomposite (BSA@AuNCs-MnO2) was constructed. Manganese dioxide (MnO2) was generated in situ on the gold clusters (BSA@AuNCs) based on the redox reaction between bovine serum albumin (BSA) and potassium permanganate (KMnO4). The fluorescence of BSA@AuNCs can be quenched by the in-situ grown MnO2, which has strong light absorption ability. It is worth noting that the quenched fluorescence of the BSA@AuNCs can be restored in the presence of glutathione (GSH), and MnO2 was reduced to Mn2+ in return. Encouragingly, 1⯵M GSH can cause a detectable fluorescence change. This sensitivity is comparable to other nanomaterials based fluorescent probes. Furthermore, this nanocomposite has obvious superiorities, such as good uniformity, simple preparation and mild reaction. The nanocomposite also has good stability and specificity, which can be further used for visualizing of intracellular GSH.
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Semiconducting conjugated polymer nanoparticles (SPNs) represent an emerging class of phototheranostic materials with great promise for cancer treatment. In this report, low-bandgap electron donor-acceptor (D-A)-conjugated SPNs with surface cloaked by red blood cell membrane (RBCM) are developed for highly effective photoacoustic imaging and photothermal therapy. The resulting RBCM-coated SPN (SPN@RBCM) displays remarkable near-infrared light absorption and good photostability, as well as high photothermal conversion efficiency for photoacoustic imaging and photothermal therapy. Particularly, due to the small size (< 5 nm), SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity. The RBCM endows the SPNs with prolonged systematic circulation time, less reticuloendothelial system uptake and reduced immune-recognition, hence improving tumor accumulation after intravenous injection, which provides strong photoacoustic signals and exerts excellent photothermal therapeutic effects. Thus, this work provides a valuable paradigm for safe and highly efficient tumor photoacoustic imaging and photothermal therapy for further clinical translation.
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A simple approach for constructing theranostic nanobeads is developed by using doxorubicin as a phase transfer agent to solubilize small iron oxide nanoclusters. The nanobeads can be specifically internalized into cancer cells with the guidance of an external magnetic field, resulting in good MRI and chemotherapy.
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Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Compostos Férricos/química , Nanopartículas Metálicas/química , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Liberação Controlada de Fármacos , Tratamento Farmacológico/métodos , Feminino , Compostos Férricos/administração & dosagem , Células HeLa , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Interações Hidrofóbicas e Hidrofílicas , Injeções Intravenosas , Fenômenos Magnéticos , Imageamento por Ressonância Magnética/métodos , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Correction for 'Vehicle-saving theranostic probes based on hydrophobic iron oxide nanoclusters using doxorubicin as a phase transfer agent for MRI and chemotherapy' by Yanbing Cao et al., Chem. Commun., 2019, DOI: .
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Fabricating multifunctional theranostic nanoparticles is highly pursued but still challenging for effective cancer treatment. Herein is reported a new theranostic nanoagent as both an MRI and targeted chemo/photothermal therapeutic agent. Prussian blue nanoparticles (PB) were first decorated with polydopamine (PDA), then conjugated with polyethylene glycol (PEG) and folic acid (FA), and finally loaded with doxorubicin (DOX) (denoted as PB@PDA@PEG-FA-DOX). The nanoagent was estimated to have an average size of 40 nm with a DOX-loading capacity of 36%, photothermal conversion efficiency of 45.7% and a transverse relaxation rate of 0.366 mM-1 s-1. In vitro release investigations showed a dual-responsive release by a mild acid and near-infrared (NIR) laser irradiation. PB@PDA@PEG-FA illustrated negligible cytotoxicity against the HL-7702 cell line and 38.2% cell viability under NIR against the HeLa cell line. PB@PDA@PEG-FA-DOX exhibited 45.2% cell viability. In contrast, the cell viability of PB@PDA@PEG-FA-DOX was dramatically decreased to 18.4% under NIR. Exclusive of folic acid, PB@PDA@PEG-DOX demonstrated 40.5% cell viability. These results demonstrated the potential of the nanoagent for integrated photothermal therapy (PTT) and chemotherapy, also embracing the FA targeting effect. In vivo MRI confirmed the effective nanoparticle accumulation, while infrared thermal images revealed the dramatically increased temperature under NIR at a tumor site. In vivo combination treatment-induced tumors were nearly completely destroyed without significant body weight loss after 14 days. H&E and Ki67 staining indicated remarkable necrosis and weak cell proliferation in the tumor area. Histologic examination revealed a lower toxicity in the vital organs. Therefore, this combination of chemo/photothermal therapy could provide an efficient route for cancer treatment.
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Ferrocianetos/química , Ácido Fólico/química , Indóis/química , Imageamento por Ressonância Magnética/métodos , Terapia de Alvo Molecular , Nanopartículas/química , Fototerapia/métodos , Polímeros/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacocinética , Células HeLa , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Polietilenoglicóis/química , Distribuição TecidualRESUMO
Tumor microenvironment activated nanodevices have remarkable superiority to enhance therapeutic efficacy and minimize side effects, but their practical applications are dramatically reduced by the low abundance and heterogeneous distribution of specific stimuli at the tumor site. Herein, programmable vesicular nanodevices based on the triblock copolymer containing poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) with peroxalate esters (PO) as hydrogen peroxide-responsive linkage (PEG-PO-PCL-PO-PEG), are developed for co-delivery of hypoxia-activated prodrug (AQ4N) and glucose oxidase (GOD). The obtained nanodevices (PAG) can be activated by the high level of H2 O2 in tumor microenvironment to improve the permeability of membranes for glucose entrance. Afterward, the oxidation of glucose catalyzed by GOD produces amplified H2 O2 amounts which in turn induce complete destruction of PAG for fast release of AQ4N and GOD. Ultimately, the PAG can exert programmable therapeutic effects from the following aspects: 1) starvation therapy by cutting off the energy supply from glucose through GOD catalysis; 2) oxidative cytotoxicity after H2 O2 amplification; 3) chemotherapy of AQ4N activated by the intensified tumor hypoxia microenvironment after oxygen consumption. The stimuli amplification, controlled drug release, synergistic therapy, and corresponding mechanisms of PAG are demonstrated. Therefore, the presented work could provide significant new insights for cancer treatment.
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Peróxido de Hidrogênio/metabolismo , Nanotecnologia/métodos , Microambiente Tumoral , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glucose/química , Glucose/metabolismo , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Nus , Nanotecnologia/instrumentação , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Poliésteres/química , Polietilenoglicóis/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Carbonilação ProteicaRESUMO
Theranostic nanoprobes integrated with dual-modal imaging and therapeutic functions, such as photodynamic therapy (PDT), have exhibited significant potency in cancer treatments due to their high imaging accuracy and non-invasive advantages for cancer elimination. However, biocompatibility and highly efficient accumulation of these nanoprobes in tumor are still unsatisfactory for clinical application. In this study, a photosensitizer -loaded magnetic nanobead with surface further coated with a layer of cancer cell membrane (SSAP-Ce6@CCM) was designed to improve the biocompatibility and cellular uptake and ultimately achieve enhanced MR/NIR fluorescence imaging and PDT efficacy. Compared with similar nanobeads without CCM coating, SSAP-Ce6@CCM showed significantly enhanced cellular uptake, as evidenced by Prussian blue staining, confocal laser scanning microscopy (CLSM) and flow cytometric analysis. Consequently, SSAP-Ce6@CCM displayed a more distinct MR/NIR imaging ability and more obvious photo-cytotoxicity towards cancer cells under 670 nm laser irradiation. Furthermore, the enhanced PDT effect benefited from the surface coating of cancer cell membrane was demonstrated in SMMC-7721 tumor-bearing mice through tumor growth observation and tumor tissue pathological examination. Therefore, this CCM-disguised nanobead that integrated the abilities of MR/NIR fluorescence dual-modal imaging and photodynamic therapy might be a promising theranostic platform for tumor treatment.