23 research outputs found
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Resource uptake and host tissue chemistry: Implications for competition and disease
Maintenance of optimal nutrient supplies is fundamental to the functioning of
vertebrate, invertebrate, bacterial and plant physiology. Organisms on this planet compete
with each other primarily to fulfill nutritional needs in order to maximize their health,
wellbeing, and reproductive success. Here we examine nutrient concentrations in several
different grass species within the context of the causes and effects of infection by barley
yellow dwarf viruses, a common and economically important pathogen of grasses
worldwide. Here we examine whether there is evidence that nutrient concentration
motivates the vector to seek and feed on particular grasses. We selected grass species for
which we knew aphid fecundity from a previous experiment. We analyzed tissue from
these plants to determine their carbon to nitrogen ratios. We found that perennial grasses
contained more tissue carbon than annuals, regardless of fertilization, and fertilized
annual grasses increased more in tissue nitrogen than did the perennial grass species.
These results are concordant with previous findings: aphids preferred and produced more
offspring on the lower carbon annual grasses, suggesting that aphid vector preference and
performance may be controlled by nutrition
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Dendrimer-encapsulated naphthalocyanine as a single agent-based theranostic nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy
Multifunctional theranostic platforms capable of concurrent near-infrared (NIR) fluorescence imaging and phototherapies are strongly desired for cancer diagnostic and treatment. However, integration of separate imaging and therapeutic components into nanocarriers results in complex theranostic systems with limited translational potential. A single agent-based theranostic nanoplatform, therefore, was developed for concurrent NIR fluorescence imaging and combinatorial phototherapy with dual photodynamic (PDT) and photothermal (PTT) therapeutic mechanisms. The transformation of substituted silicon naphthalocyanine (SiNc) into biocompatible nanoplatform (SiNc-NP) was achieved by SiNc encapsulation into the hydrophobic interior of the generation 5 polypropylenimine dendrimer following surface modification with polyethylene glycol. Encapsulation provides aqueous solubility to SiNc and preserves its NIR fluorescence, PDT and PTT properties. Moreover, impressive photostability of dendrimer-encapsulated SiNc have been detected. Under NIR irradiation (785 nm, 1.3 W/cm²), SiNc-NP manifested robust heat generation capability (ΔT = 40 °C) and efficiently produced reactive oxygen species essential for PTT and PDT, respectively, without releasing SiNc from
the nanopaltform. By varying laser power density from 0.3 W/cm² to 1.3 W/cm² the therapeutic mechanism of SiNc-NP could be switched from PDT to combinatorial PDT-PTT treatment. In vitro and in vivo studies confirmed that phototherapy mediated by SiNc can efficiently destroy chemotherapy resistant ovarian cancer cells. Remarkably, solid tumors treated with a single dose of SiNc-NP combined with NIR irradiation were completely eradicated without cancer recurrence. Finally, the efficiency of SiNc-NP as an NIR imaging agent was confirmed by recording the strong fluorescence signal in the tumor, which was not photobleached during the phototherapeutic procedure.Keywords: photothermal therapy, photostability, near-infrared imaging, theranostic, naphthalocyanine, photodynamic therap
Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin
Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks
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Multifunctional Nanomedicine Platform for Concurrent Delivery of Chemotherapeutic Drugs and Mild Hyperthermia to Ovarian Cancer Cells
A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40 °C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/international-journal-of-pharmaceutics/.Keywords: Mild hyperthermia, Iron oxide nanoparticles, Ovarian cancer, Combinatorial treatment, Alternating magnetic field (AMF), Doxorubici
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Naphthalocyanine-Based Biodegradable Polymeric Nanoparticles for Image-Guided Combinatorial Phototherapy
Image-guided phototherapy is extensively considered as a promising therapy for cancer treatment. To enhance translational potential of this modality, we developed a single agent-based biocompatible nanoplatform that provides both real time near-infrared (NIR) fluorescence imaging and combinatorial phototherapy with dual photothermal and photodynamic therapeutic mechanisms. The developed theranostic nanoplatform consists of two building blocks: (1) silicon naphthalocyanine (SiNc) as NIR fluorescence imaging and phototherapeutic agent and (2) a copolymer, poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) as the biodegradable SiNc carrier. Our simple, highly reproducible and robust approach results in preparation of spherical, monodisperse SiNc-loaded PEG-PCL polymeric nanoparticles (SiNc-PNP) with a hydrodynamic size of 37.66 ± 0.26 nm (polydispersity index = 0.06) and surface charge of -2.76 ± 1.83 mV. The SiNc-loaded nanoparticles exhibit a strong NIR light absorption with an extinction coefficient of 2.8 x 10⁵ M⁻¹cm⁻¹ and efficiently convert the absorbed energy into fluorescence emission (Φ[subscript F] = 11.8%), heat (ΔT ~ 25 °C) and reactive oxygen species. Moreover, the SiNc-PNP are characterized by superior photostability under extensive photoirradiation and structure integrity during storage at room temperature over a period of 30 days. Following intravenous injection, the SiNc-PNP accumulated selectively in tumors and provided high lesion-to-normal tissue contrast for sensitive fluorescence detection. Finally, Adriamycin-resistant tumors treated with a single intravenous dose of SiNc-PNP (1.5 mg/kg) combined with 10 min of a 785 nm light irradiation (1.3 W/cm²) were completely eradicated from the mice without cancer recurrence or side effects. The reported characteristics make the developed SiNc-PNP a promising platform for future clinical application.This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society and can be found at: https://doi.org/10.1021/acs.chemmater.5b0312
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ROS-Induced Nanotherapeutic Approach for Ovarian Cancer Treatment Based on the Combinatorial Effect of Photodynamic Therapy and DJ-1 Gene Suppression
This study represents a novel approach for intraoperative ovarian cancer treatment based on the combinatorial effect of a targeted photodynamic therapy (PDT) associated with suppression of the DJ-1 protein, one of the key players in the ROS defense of cancer cells. To assess the potential of the developed therapy, dendrimer-based nanoplatforms for cancer-targeted delivery of near-infrared photosensitizer, phthalocyanine, and DJ-1 siRNA have been constructed. In vitro studies revealed that therapeutic efficacy of the combinatorial approach was enhanced when compared to PDT alone and this enhancement was more pronounced in ovarian carcinoma cells, which are characterized by higher basal levels of DJ-1 protein. Moreover, the ovarian cancer tumors exposed to a single dose of combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence. Thus, the developed therapeutic approach can be potentially employed intraoperatively to eradicate unresactable cancer cells.Keywords: DJ-1, ovarian cancer, ROS, photodynamic therapy, siRNA therapyKeywords: DJ-1, ovarian cancer, ROS, photodynamic therapy, siRNA therap
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Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin
Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks
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A Nanoparticle Mediated Gene Silencing Approach for the Treatment of Metastatic Ovarian Cancer
Ovarian cancer, “the silent killer,” is one of the deadliest gynecological diseases due to delayed diagnosis, leading to a heavily disseminated and aggressive metastatic cancer. Therapeutic options are limited at stages III-IV of ovarian cancer, in which debulking surgery and cytotoxic chemotherapy remain the mainstays of
intervention. However, these therapeutic modalities are not adequate: the 5-year mortality rates for stages III-IV ovarian cancer are extremely abysmal, providing only 17% survival rates for patients after treatment. Therefore, there is a dire need for new therapeutic modalities to treat this disease and improve quality of life of patients as they undergo chemotherapy. PARK7/DJ-1 is an oncogenic driver protein in numerous cancers. DJ-1 plays a fundamental role in the growth, survival, and proliferation in cancer. However, targeting of DJ-1 for therapeutic gain in ovarian cancer has not been previously reported. I have designed a nanoparticle-based platform that delivers DJ-1 siRNA to ovarian cancer cells. This system effectively silences DJ-1 expression and suppresses ovarian cancer growth in vitro and in vivo. Further, I have shown that a knockdown of DJ-1 causes an increase in intracellular reactive oxygen species (ROS), and this renders the cancer cells more vulnerable to agents inducing oxidative stress through multiple signaling pathways
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Temperature-Tunable Iron Oxide Nanoparticles for Remote-Controlled Drug Release
Herein, we report the successful development of a novel nanosystem capable of an efficient delivery and temperature-triggered drug release specifically aimed at cancer. The water-soluble 130.1 ± 0.2 nm iron oxide nanoparticles (IONPs) were obtained via synthesis of a monodispersed iron oxide core stabilized with tetramethylammonium hydroxide pentahydrate (TMAOH), followed by coating with the thermoresponsive copolymer poly-(NIPAM-stat-AAm)-block-PEI (PNAP). The PNAP layer on the surface of the IONP undergoes reversible temperature-dependent structural changes from a swollen to a collapsed state resulting in the controlled release of anticancer drugs loaded in the delivery vehicle. We demonstrated that the phase transition temperature of the prepared copolymer can be precisely tuned to the desired value in the range of 36-44 °C by changing the monomers ratio during the preparation of the nanoparticles. Evidence of modification of the IONPs with the thermoresponsive copolymer is proven by ATR-FTIR and a quantitative analysis of the polymeric and iron oxide content obtained by thermogravimetric analysis. When loaded with doxorubicin (DOX), the IONPs-PNAP revealed a triggered drug release at a temperature that is a few degrees higher than the phase transition temperature of a copolymer. Furthermore, an in vitro study demonstrated an efficient internalization of the nanoparticles into the cancer cells, and showed that the drug-free IONPs-PNAP were nontoxic toward the cells. In contrast, sufficient therapeutic effect was observed for the DOX-loaded nanosystem as a function of temperature. Thus, the developed temperature-tunable IONPs-based delivery system showed high potential for remotely triggered drug delivery and the eradication of cancer cells.Keywords: Tunable LCST, Thermoresponsive copolymer, Remote-triggered drug release, IONPs, Drug deliver