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The combination of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhancing ROS-mediated cancer treatment. Herein, we reported an in situ polymerized hollow mesoporous organosilica nanoparticle (HMON) biocatalysis nanoreactor to integrate the synergistic effect of PDT/CDT for enhancing ROS-mediated pancreatic ductal adenocarcinoma treatment. HPPH photosensitizer was hybridized within the framework of HMON via an "in situ framework growth" approach. Then, the hollow cavity of HMONs was exploited as a nanoreactor for "in situ polymerization" to synthesize the polymer containing thiol groups, thereby enabling the immobilization of ultrasmall gold nanoparticles, which behave like glucose oxidase-like nanozyme, converting glucose into H2O2 to provide self-supplied H2O2 for CDT. Meanwhile, Cu2+-tannic acid complexes were further deposited on the surface of HMONs (HMON-Au@Cu-TA) to initiate Fenton-like reaction to covert the self-supplied H2O2 into â¢OH, a highly toxic ROS. Finally, collagenase (Col), which can degrade the collagen I fiber in the extracellular matrix (ECM), was loaded into HMON-Au@Cu-TA to enhance the penetration of HMONs and O2 infiltration for enhanced PDT. This study provides a good paradigm for enhancing ROS-mediated anti-tumor efficacy. Meanwhile, this research offers a new method to broaden the application of silica based nanotheranostics.
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Combination of upconversion nanocrystals (UCNs) with CeO2 is a decent choice to construct NIR-activated photocatalysts for utilizing the NIR light in the solar spectrum. Herein we present a facile approach to deposit a CeO2 layer with controllable thickness on the plate-shaped NaYF4:Yb,Tm UCNs. The developed core-shell nanocomposites display obvious photocatalytic activity under the NIR light and exhibit enhanced activity under the full solar spectrum. For enhancing the separation of photogenerated electrons and holes on the CeO2 surface, we sequentially coat a ZnO shell on the nanocomposites so as to form a heterojunction structure for achieving a better activity. The developed hybrid photocatalysts have been characterized with TEM, SEM, PL, etc., and the working mechanism of such UCN-semiconductor heterojunction photocatalysts has been proposed.
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Tumor hypoxia is responsible for the reduced therapeutic efficacy of type II photodynamic therapy (PDT) because of the dependence of cellular oxygen during 1O2 generation. Type I PDT may be a better strategy to overcome the disadvantages of hypoxia for enhanced theranostics. Herein, a new semiconducting polymer PDPP was synthesized and encapsulated with hydrophilic PEG-PDPA to enhance the electron transfer for type I PDT. PDPP NPs show a high superoxide radical generation ability with DHR123 as a probe. In vitro MTT assay indicates PDPP NPs with considerably high phototoxicity on human cervical cancer cells (HeLa) with a low half-maximal inhibitory concentration (IC50) of 6.1 µg/ml. Furthermore, an in vivo study demonstrates that PDPP NPs can lead to complete tumor suppression with the help of laser, compared with the control and dark groups. The biosafety is confirmed by the H&E analysis of the normal tissues (the heart, liver, spleen, lungs, and kidney). The results provide a strategy to design nanosystems for type I PDT and PTT synergistic therapy.
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Controllable self-assembly of photonic molecules for precise biomedicine is highly desirable but challenging to prepare multifunctional nano-phototheranostics. Herein, we developed a generic self-assembly approach to design nano-phototheranostics that provides NIR-II fluorescence imaging and phototherapy. We first designed and synthesized two amphiphilic photonic molecules, PEG2000-IR806 and BODIPY. Then, we prepared the co-self-assembled phototheranostic agents, PEG2000-IR806/BODIPY nanoparticles (PIBY NPs). The morphology of the PIBY NPs is controllable by adjusting the ratio of PEG2000-IR806 and BODIPY during self-assembly. The NIR-II fluorescence properties and phototherapy capability of the PIBY NPs were demonstrated in vitro and in vivo. By tuning the ratio of PEG2000-IR806 and BODIPY, the PIBY NPs showed various morphologies (e.g. spherical nanoparticles, nanovesicles and rod-like nanoparticles). The PEG2000-IR806 plays two roles in the co-self-assemblies, one is second near-infrared (NIR-II, 1000-1700 nm) agent, the other is the surfactant for BODIPY encapsulation. The phototherapeutic PIBY NPs all show bright NIR-II fluorescence and effective phototherapeutic (photothermal and photodynamic) properties, which are attributed to IR806 and BODIPY, respectively. The driving force of the self-assembly can be attributed to the electrostatic interaction between NIR806 and BODIPY and their hydrophobicity. The rod-like PIBY NPs (rPIBY NPs) demonstrated a low half inhibitory concentration (IC50) of 3.96 µg/mL on U87MG cells. The NIR-II imaging showed the accumulation of rPIBY NPs in the tumor region. After systemic injection of rPIBY NPs at low dose (0.5 mg/kg), the tumor growth was greatly inhibited upon laser irradiation without noticeable side effects. This study provides a generic self-assembly approach to fabricate NIR-II imaging and phototherapeutic platform for cancer phototheranostics. STATEMENT OF SIGNIFICANCE: Nanophototheranostics providing NIR-II fluorescence imaging and phototherapy are expected to play a critical role in modern precision medicine. Controllable self-assembly of optical molecules for the fabrication of efficient nanophototheranostics is highly desirable but challenging. This work reports for the first time the co-assembly of a NIR-II imaging contrast agent and a phototherapeutic agent to yield nanophototheranostics with various morphologies. The design of molecular co-assembly with complementary optical functions can be a generic method for future the development of phototheranostics.
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Nanopartículas , Neoplasias , Línea Celular Tumoral , Humanos , Nanopartículas/uso terapéutico , Imagen Óptica , Fototerapia , Medicina de Precisión , Nanomedicina Teranóstica/métodosRESUMEN
Converting CO2 into high-valued chemicals with sunlight is regarded as a promising way to solve the impending energy and environmental crisis. Development of efficient photocatalysts with suitable energy band gap, high stability and favorable structure is thus of very importance. Herein, a novel hierarchical Bi2WO6 photocatalyst assembled by Bi2WO6 nanosheets with a hollow and rod-shaped appearance has been developed via a facile hydrothermal process. Interestingly, we found that the hydrolysis of Bi(NO3)3 in water can produce solid Bi6O5(OH)3(NO3)5·3H2O microrods which can be transformed to hollow-hierarchical Bi2WO6 nanosheets by virtue of the Kirkendall effect. The developed Bi2WO6 nanosheets exhibit a 58 times higher specific surface area than that of bulk Bi2WO6 and a remarkable enhancement in electrochemical performance such as photocurrent and charge transfer. As a result, the hollow-hierarchical structured Bi2WO6 photocatalysts achieve a high CH4 yield of 2.6⯵molâ¯g-1â¯h-1, 8 times higher than that of bulk Bi2WO6. Moreover, the developed photocatalysts exhibit a high stability during the recycling experiments. This work may present a new strategy to attain hierarchical structured photocatalysts with high activity and stability toward CO2 reduction.
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Cartilage degeneration is the hallmark of osteoarthritis (OA) and its early diagnosis is essential for effective cartilage repair. However, until now, there was still a lack of imaging modalities that can accurately detect and evaluate cartilage degeneration in its early stage. Herein, we introduce endogenous melanin nanoparticles (MNPs) encapsulated by poly-l-lysine (PLL) as positively charged contrast agents for the accurate photoacoustic (PA) imaging of cartilage degeneration through its strong electrostatic interaction with anionic glycosaminoglycans (GAGs) in the cartilage. PLL-MNPs presented high PA intensity, photostability and biocompatibility. In vitro PAI studies showed that PLL-MNPs with a zeta potential of +32.5 ± 9.3 mV had more cartilage uptake and longer retention time than anionic MNPs, and generated a positive relationship with the GAG content in the cartilage. After administration via intra-articular injection in living mouse models, PLL-MNPs exhibited about a two-fold stronger PA signal in a normal joint (with high GAG content) than an OA joint (with low GAG content). Furthermore, the obtained PAI results provided accurate information of the GAG content distribution in the OA knee joint. Consequently, by detecting and analyzing the changes of the GAG content in OA cartilage using PAI, we can clearly distinguish early OA from late OA and monitor the therapeutic efficacy in OA after drug treatment. All PAI results were examined histologically.
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Medios de Contraste/química , Glicosaminoglicanos/química , Melaninas/química , Osteoartritis/diagnóstico por imagen , Técnicas Fotoacústicas , Polilisina/química , Animales , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Diagnóstico Precoz , Masculino , Ratones , Células 3T3 NIH , NanopartículasRESUMEN
Development of MOF-based photocatalysts is intriguing research due to their structural flexibility and tremendous catalytic sites, whereas most MOFs only can take use of UV/visible light and lack of response to NIR light. Herein, we present a facile approach to integrate upconversion nanoparticles (UCNPs) with MOF to build a NIR-responsive composite photocatalyst. The MOF shell with controllable thickness can be grown on the UCNPs, thus exhibiting tunable photocatalytic activities under NIR irradiation. Furthermore, we extend visible absorption of the MOF shell by adding -NH2 groups so that the composite photocatalysts have a better utilization of UC emissions and sunlight to improve their activities. The developed composite photocatalysts have been characterized by XRD, TEM, PL, etc., and their photocatalytic performances were systematically explored. The formation and working mechanism of the composite photocatalysts were also elucidated.
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CXCL5, a CXC-type chemokine, is an important attractant for granulocytic immune cells by binding to its receptor CXCR2. Recently, CXCL5/CXCR2 has been found to play an oncogenic role in many human cancers. However, the exact role of CXCL5 in osteosarcoma cell migration and invasion has not been revealed. Here we found that the protein expression of CXCL5 was significantly increased in osteosarcoma tissues compared with that in matched adjacent nontumor tissues. Moreover, the expression of CXCL5 was significantly associated with advanced clinical stage and metastasis. Further investigation showed that the CXCL5 expression levels were also significantly increased in osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared with those in normal osteoblast hFoB1.19 cells. U2OS cells were further transfected with CXCL5-specific siRNA or overexpression plasmid. Knockdown of CXCL5 significantly suppressed U2OS cell migration and invasion. On the contrary, overexpression of CXLC5 remarkably promoted the migration and invasion of U2OS cells. Interestingly, both exogenous CXCL5 treatment and the conditioned medium of CXCL5-overexpressing hFoB1.19 cells could also enhance the migration and invasion of U2OS cells, suggesting that the promoting role of CXCL5 in U2OS cell migration and invasion is also in a paracrine-dependent manner. According to these data, our study demonstrates that CXCL5 is upregulated in osteosarcoma and may play an oncogenic role in osteosarcoma metastasis. Therefore, CXCL5 may become a potential therapeutic target for osteosarcoma treatment.
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Comunicación Autocrina/fisiología , Movimiento Celular/fisiología , Quimiocina CXCL5/fisiología , Invasividad Neoplásica/patología , Osteosarcoma/patología , Comunicación Paracrina/fisiología , Línea Celular Tumoral , Humanos , Osteosarcoma/metabolismoRESUMEN
Acute venous thrombosis is prevalent and potentially fatal. Accurate diagnosis of early thrombus is needed for patients in timely clinical intervention to prevent life-threatening conditions. Photoacoustic imaging (PAI) with excellent spatial resolution and high optical contrast shows more promise for this purpose. However, its application is dramatically limited by its signal-off effect on thrombus because of the ischemia in thrombus which lacks the endogenous photoacoustic (PA) signal of hemoglobin. To address this dilemma, we herein report the feasibility of using organic semiconducting nanoparticles (NPs) for contrast-enhanced PAI of thrombus in living mice. An organic semiconducting NP, self-assembled by amphiphilic perylene-3,4,9,10-tetracarboxylic diimide (PDI) molecules, is chemically modified with cyclic Arg-Gly-Asp (cRGD) peptides as a PA contrast agent (cRGD-PDI NPs) for selectively lightening early thrombus. cRGD-PDI NPs presents high PA intensity, good stability in light and serum, and sufficient blood-circulating half-life. In living mice, PA intensity of early thrombus significantly increases after tail vein injection of cRGD-PDI NPs, which is 4-fold greater than that of the control, blocking, and old thrombus groups. Pathological and immunohistochemical findings show that glycoprotein IIb/IIIa abundant in early thrombus is a good biomarker targeted by cRGD-PDI NPs for distinguishing early thrombus from old thrombus by PAI. Such a lightening PAI effect by cRGD-PDI NPs successfully provides accurate information including the profile, size and conformation, and spatial distribution of early thrombus, which may timely monitor the obstructive degree of thrombus in blood vessels and the thrombolysis effect.
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Medios de Contraste/química , Imidas/química , Nanopartículas/química , Imagen Óptica , Perileno/análogos & derivados , Técnicas Fotoacústicas , Trombosis/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Oligopéptidos/química , Tamaño de la Partícula , Perileno/química , Semiconductores , Propiedades de Superficie , Tensoactivos/químicaRESUMEN
<p><b>OBJECTIVE</b>To study the effect of Gardenia-Aweto compound (GAC) and two component on preventing acute respiratory distress syndrome (ARDS) by the rabbit model of ARDS induced by intravenous injection of oleic acid. To detect the efficiency component of GAC in preventing ARDS.</p><p><b>METHOD</b>GAC was divided into two compounts, ethanol-soluble components (ESC) and ethanol-deposition components (EDC), based on polarity. Forty-three new zealand rabbits were randomly divided into five groups, the blank control group, the model group, the GAC groups, the ESC group, and the EDC group. The ARDS model was induced by intravenous injection of oleic acid. Dynamic changes of arterial blood gas, lung index, albumin in bronchoalveolar lavage fluid (BALF) in different groups and lung histological changes were observed and compared.</p><p><b>RESULT</b>As compared with the blank group, in the model group, GAC group, ESC group, EDC group the arterial PO2 and oxygen saturation deprived continuously. While SO2 in GAC group at time points 30, 60, 90, 120 min (P < 0.05 or 0.01) and SO2 in ESC group at time points 30, 60, 90 min were higher than those in ARDS group. PO2 in ESC group at time points 30, 60 min (P < 0.05) were higher than those in ARDS group. The value of LI and W/D were higher in ARDS group than in sham group (P < 0.01), they were much lower in HD group than in ARDS group (P < 0.01). Concentration of BALF-albumin increased markedly in ARDS group and pre-treatment groups compared with sham group, but it was much lower in GAC group and ESC group, there was a significant difference between GAC group (P < 0.01), ESC group (P < 0.05) and ARDS group. The lung histological changes had been improved in GAC group and ESC group. But no significantly difference between above-mentioned parameters was found in comparison in the model group and in the EDC group.</p><p><b>CONCLUSION</b>Preventive administration of GAC or ESC an protect the damaged lung function in ARDS rabbits induced by oleic acid. The efficiency component of GAC in preventing ARDS is ESC. GAC antagonizing ARDS may relate to its anti-inflammatory, immuno-modulatory, anti-oxidant and antithrombotic effects.</p>
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Animales , Femenino , Masculino , Conejos , Cordyceps , Química , Combinación de Medicamentos , Medicamentos Herbarios Chinos , Usos Terapéuticos , Gardenia , Química , Lepidópteros , Materia Medica , Usos Terapéuticos , Ácido Oléico , Fitoterapia , Intercambio Gaseoso Pulmonar , Distribución Aleatoria , Síndrome de Dificultad Respiratoria , PatologíaRESUMEN
<p><b>OBJECTIVES</b>To evaluate the efficacy of a hybrid artificial liver support system in the treatment of chronic severe hepatitis.</p><p><b>METHODS</b>The hybrid artificial liver support system (HALSS) consisted of a bioreactor containing more than 5 x 10(9) porcine hepatocytes and plasma exchange device. 15 patients with chronic severe viral hepatitis were treated with the hybrid system.</p><p><b>RESULTS</b>All the patients experienced a reduction in symptoms, such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly (from 493.5 micromol/L+-139.8 micromol/L to 250.9 micromol/L+-91.3 micromol/L, t=8.695, P<0.001), while prothrombin activity increased (from 24.5%+-8.4% to 30.6%+-6.3%, t=3.325, P<0.01). There were 11 patients whose progress of hepatocytes necrosis stopped after HALSS treatment, and finally they recovered completely. Four patients died of their worsen conditions. No serious adverse events were noted in the 15 patients.</p><p><b>CONCLUSION</b>HALSS is a reliable hepatic support device for chronic severe hepatitis.</p>