- Targeted Delivery of Functionalized Upconversion Nanoparticles for Externally Triggered Photothermal/Photodynamic Therapies of Brain Glioblastoma. [Journal Article]
- TTheranostics 2018; 8(5):1435-1448
- Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. I...
Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work. Methods: The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers. The hybrid nanoparticles (ANG-IMNPs) were characterized by DLS, TEM, UV/vis and fluorescence spectrophotometer. Cellular uptake was examined by laser scanning confocal microscopy and flow cytometry. The PDT/PTT effect of ANG-IMNPs was evaluated using MTT assay. Tumor accumulation of NPs was determined by a non-invasive in vivo imaging system (IVIS). The in vivo anti-glioma effect of ANG-IMNPs was evaluated by immunohistochemical (IHC) examination of tumor tissues and Kaplan-Meier survival analysis. Results: In vitro data demonstrated enhanced uptake of ANG-IMNPs by murine astrocytoma cells (ALTS1C1) and pronounced cytotoxicity by combined NIR-triggered PDT and PTT. In consistence with the increased penetration of ANG-IMNPs through endothelial monolayer in vitro, the NPs have also shown significantly enhanced accumulation at brain tumor by IVIS. The IHC tissue examination confirmed prominent apoptotic and necrotic effects on tumor cells in mice receiving targeted dual photo-based therapies, which also led to enhanced median survival (24 days) as compared to the NP treatment without angiopep-2 (14 days). Conclusion: In vitro and in vivo data strongly indicate that the ANG-IMNPs were capable of selectively delivering dual photosensitizers to brain astrocytoma tumors for effective PDT/PTT in conjugation with a substantially improved median survival. The therapeutic efficacy of ANG-IMNPs demonstrated in this study suggests their potential in overcoming BBB and establishing an effective treatment against GBM.
- A novel flurophore-cyano-carboxylic-Ag microhybrid: Enhanced two photon absorption for two-photon photothermal therapy of HeLa cancer cells by targeting mitochondria. [Journal Article]
- BBBiosens Bioelectron 2018 Jun 15; 108:14-19
- In this study, a novel two-photon photothermal therapy (TP-PTT) agent based on an organic-metal microhybrid with surface Plasmon resonance (SPR) enhanced two-photon absorption (TPA) characteristic wa...
In this study, a novel two-photon photothermal therapy (TP-PTT) agent based on an organic-metal microhybrid with surface Plasmon resonance (SPR) enhanced two-photon absorption (TPA) characteristic was designed and synthesized using a fluorescent cyano-carboxylic derivative 2-cyano-3-(9-ethyl-9H-carbazol-3-yl) -acrylic acid (abbreviated as CECZA) and silver nanoparticles through self-assembly process induced by the interfacial coordination interactions between the O/N atom of CECZA and Ag+ion at the surface of Ag nanoparticles. The coordination interactions caused electron transfer from the Ag nanoparticles to CECZA molecules at the excited state, resulting in a decreased fluorescence quantum yield. The interfacial coordination interactions also enhanced the nonlinear optical properties, including 13 times increase in the TPA cross-section (δ). The decreased fluorescence quantum yield and increased two photon absorption caused by the SPR effect led excellent two-photon photothermal conversion, which was beneficial for the TP-PTT effect on HeLa cancer cells.
- In vitro outlook of gold nanoparticles in photo-thermal therapy: a literature review. [Journal Article]
- LMLasers Med Sci 2018 Feb 28
- Hyperthermia is an anti-cancer treatment in which the temperature of the malignant tumor is increased more than other adjacent normal tissues. Microwave, ultrasound, laser, and radiofrequency sources...
Hyperthermia is an anti-cancer treatment in which the temperature of the malignant tumor is increased more than other adjacent normal tissues. Microwave, ultrasound, laser, and radiofrequency sources have been used for hyperthermia of cancerous tissues. In the past decade, near-infrared (NIR) laser for cancer therapy, known as photo-thermal therapy (PTT), was expanded in which the photo-sensitizer agent converts the light photon energy to heat. The heat following PTT can destroy cancer cells. There are some photo-sensitizer agents which have been used for PTT; however, owing to recent advances in nanotechnology, noble metal nanoparticles like gold (Au) nanoparticles (GNPs) have been used successfully in PTT. GNPs have some desirable specifications, including simple and controlled synthesis, small size, high level of biocompatibility, and surface plasmon resonance (SPR). The SPR effect of the GNPs increases the radiative properties like absorption and scattering; therefore, they can be used in PTT. In this article, we reviewed recent in vitro studies of PTT using GNPs in literature. At first, we focus on the physical properties of GNPs, their interaction with infrared radiation, and physical parameters governing the interaction of infrared radiation with the GNPs. Then, we review the passive and active targeting of GNPs using the different coating to induce the thermal damage in cancer cells using low-level laser PPT. The GNPs' cellular internalization into cancer cells is a challenge which is consequently considered. In this review, we also summarize the results of synergistic cancer therapy studies on the combination of radiation therapy as a routine cancer treatment and PTT: in which significant improvement occurs in treatment efficacy.
- Redox-responsive UCNPs-DPA conjugated NGO-PEG-BPEI-DOX for imaging-guided PTT and chemotherapy for cancer treatment. [Journal Article]
- DTDalton Trans 2018 Mar 12; 47(11):3921-3930
- The disulfide bond (-S-S-) is an enormously valuable functional group in a variety of chemical and biological agents that display effective reactivity or biological activities (e.g., antitumor activi...
The disulfide bond (-S-S-) is an enormously valuable functional group in a variety of chemical and biological agents that display effective reactivity or biological activities (e.g., antitumor activities). The disulfide bonds prevalent in proteins are somewhat oxidizing in the extracellular space; however, such disulfide bonds can rarely be found inside cells because of disulfide cleavage reactions facilitated by abundant free cellular thiols, including glutathione (GSH), which is the most important common thiol-containing small molecule. Interestingly, intracellular GSH concentrations are considerably higher in cancer cells than in analogous normal cells; this feature may prove to be significant in the development of anticancer drug delivery systems (DDS). Moreover, upconversion nanoparticles (UCNPs) have been extensively investigated in multimodal imaging, photodynamic therapy (PDT) and photothermal therapy. UCNPs exploit near-infrared excitation instead of ultraviolet excitation and possess exclusive properties, which include greatly increased penetration depth in biological samples and reductions in background autofluorescence, photobleaching and photodamage to biological specimens. These fascinating optical features of UCNPs may broaden their prospects in the fields of imaging and therapy. Graphene has emerged as a flat monolayer of carbon atoms that are tightly embedded in a two-dimensional (2D) honeycomb lattice. Widespread research has been carried out on graphene in recent years owing to its exclusive shape and size, as well as innumerable fascinating physical and chemical properties. Owing to their high optical absorption in the near-infrared (NIR) region, graphene and GO have been extensively employed for photothermal therapy (PTT). In this study, we attempted to merge the properties of these compounds by conjugating UCNPs and NGO-PEG-BPEI-DOX into a single platform for chemotherapy and photothermal therapy.
- Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice. [Journal Article]
- DDiabetologia 2018; 61(5):1180-1192
- CONCLUSIONS: The results indicate that FSH enhances CRTC2-mediated gluconeogenesis dependent on AMPK Ser485 phosphorylation via GRK2 in the liver, suggesting an essential role of FSH in the pathogenesis of fasting hyperglycaemia.
- Are Comorbid Pain and Depressive Symptoms Associated with Rehabilitation of Individuals with Spinal Cord Injury? [Journal Article]
- TSTop Spinal Cord Inj Rehabil 2018; 24(1):37-43
- Objective: To examine the difference in functional outcomes and therapy intensity among individuals with spinal cord injury (SCI) with comorbid depression and pain symptoms compared to those without...
Objective: To examine the difference in functional outcomes and therapy intensity among individuals with spinal cord injury (SCI) with comorbid depression and pain symptoms compared to those without these symptoms. Methods: A retrospective chart review was conducted of 100 patients admitted to a specialized SCI inpatient rehabilitation unit. Standard demographic factors were collected. Patients were divided into 2 groups: those with comorbid depression and pain symptoms and those without. Outcomes were compared between the 2 groups using analysis of covariance (ANCOVA). Age, gender, level of injury, severity of injury, and FIM® admission were included in the model as covariates. Main outcomes included FIM® discharge, length of stay (LOS), intensity of therapy (total physical therapy time [PTt] and total occupational therapy time [OTt]), living arrangement, and vocational status. Results: No significant difference was seen between the 2 groups in FIM® discharge or OTt; however, those in the comorbidity group required significantly greater PTt than those without (p = .002). Those in the comorbid group also spent longer in inpatient rehabilitation (p = .005). The groups did not differ in postdischarge living arrangements or vocational status. Conclusion: Inpatient rehabilitation physical therapy and LOS differ substantially among individuals with comorbid depression and pain symptoms. This comorbidity may have a negative impact on functional recovery such that individuals may require more physical therapy time and longer LOS. This may also point to the increased resources required to manage individuals with SCI and comorbid depression and pain symptoms.
- Posterior Tibial Tendon Endoscopic Debridement for Stage I and II Posterior Tibial Tendon Dysfunction. [Journal Article]
- ATArthrosc Tech 2017; 6(5):e2019-e2022
- Adult acquired flatfoot deformity (AAFD), formerly known as posterior tibial tendon (PTT) dysfunction, is one of the most common problems of the foot and ankle. It was first described as tendon failu...
Adult acquired flatfoot deformity (AAFD), formerly known as posterior tibial tendon (PTT) dysfunction, is one of the most common problems of the foot and ankle. It was first described as tendon failure but has since been revealed as ligamentous failure in addition. AAFD is a spectrum of deformities that ranges from tenosynovitis (stage I) to AAFD (stages II-IV). Regarding mild stage I and stage II disease, it was once standard to perform an open synovectomy completely removing the inflamed synovium; this procedure required a large 6-cm medial ankle incision. Postoperative management included plaster cast immobilization for 3 weeks, followed by a boot with controlled ankle movement for another 3 weeks. Now, the standard is shifting to PTT endoscopy, which has proved to be an efficient way to treat tenosynovitis in stage I and II AAFD with a shorter postoperative period. Using this technique, we can achieve 360° visualization of the PTT within the tendon sheath, allowing for a complete exploration and debridement. We hope that by using this video description, practitioners could avoid the increased morbidity associated with open procedures, as well as help patients return to activity sooner after surgery.
- Preoperative coagulation abnormalities as a risk factor for adverse events after pancreas surgery. [Journal Article]
- JSJ Surg Oncol 2018 Jan 22
- CONCLUSIONS: Prolonged bleeding times (high INR/PTT) is associated with increased mortality and adverse outcomes after pancreas surgery. A patient's coagulation profile may serve as a risk stratification tool to identify higher risk patients that require more resources.
- Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles. [Review]
- CCancers (Basel) 2017 Dec 19; 9(12)
- Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalit...
Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment.
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- [Exposure to toxic dose of adrenaline on the functional state of the liver]. [Journal Article]
- PFPatol Fiziol Eksp Ter 2017 Apr-Jun; 61(2):67-71
- The blood biochemical parameters characterizing the functional state of the liver, and the morphological profile of the body after a single exposure to a toxic dose of adrenaline were studied.
The blood biochemical parameters characterizing the functional state of the liver, and the morphological profile of the body after a single exposure to a toxic dose of adrenaline were studied.