Iron Hydroxide/Oxide-Reduced Graphene Oxide Nanocomposite for Dual-Modality Photodynamic and Photothermal Therapy In Vitro and In Vivo.

Minimal invasive phototherapy utilising near-infrared (NIR) laser to generate local reactive oxygen species (ROS) and heat has few associated side effects and is a precise treatment in cancer therapy. However, high-efficiency and safe phototherapeutic tumour agents still need developing. The application of iron hydroxide/oxide immobilised on reduced graphene oxide (FeOxH-rGO) nanocomposites as a therapeutic agent in integration photodynamic cancer therapy (PDT) and photothermal cancer therapy (PTT) was discussed. Under 808 nm NIR irradiation, FeOxH-rGO offers a high ROS generation and light-to-heat conversion efficiency because of its strong NIR absorption. These phototherapeutic effects lead to irreversible damage in FeOxH-rGO-treated T47D cells. Using a tumour-bearing mouse model, NIR ablated the breast tumour effectively in the presence of FeOxH-rGO. The tumour treatment response was evaluated to be 100%. We integrated PDT and PTT into a single nanodevice to facilitate effective cancer therapy. Our FeOxH-rGO, which integrates the merits of FeOxH and rGO, displays an outstanding tumoricidal capacity, suggesting the utilization of this nanocomposites in future medical applications.

Achyranthes bidentata polypeptides promotes migration of Schwann cells via NOX4/DUOX2-dependent ROS production in rats.

Achyranthes bidentata polypeptides (ABPP), an active polypeptides isolated from the aqueous extract of Achyranthes bidentata Blume, contributes to the regeneration of injured peripheral nerves by promoting migration of Schwann cells (SCs). In this study, we aimed to investigate the possible mechanism underlying the ABPP-induced migration of primary cultured rat SCs. Transwell migration assays indicated that ABPP promoted SCs migration in a concentration-dependent manner by inducing production of NADPH-oxidase (NOX)-derived reactive oxygen species (ROS). Inhibition of ROS production by NOXs inhibitor apocynin (APO) or diphenyleneiodonium (DPI) partially blocked ABPP-mediated SCs migration. Furthermore, by using real-time polymerase chain reaction analysis and siRNA interference technique, we verified the participation of NOX subunit 4 (NOX4) and dual oxidase 2 (DUOX2) in ABPP-induced ROS production and consequential SCs migration. Taken together, these results demonstrated that ABPP promoted SCs migration via NOX4/DUOX2-activated ROS in SCs.

Photothermally controlled drug release system with high dose loading for synergistic chemo-photothermal therapy of multidrug resistance cancer.

Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO2-DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading. Benefiting from the thick layer and large pore size, the encapsulation and loading efficiency were as high as 97.7% and 8.84%, respectively. Furthermore, under the trigger of 808 nm near infrared (NIR) light, the released DOX increased significantly at pH 5.0 and reached to 39.0% in 20 min, achieving a facile intelligent control of chemotherapy additional to the photothermal therapy. The viability of MCF-7/ADR cells could be efficiently reduced to 16.9%, demonstrating the proposed photothermally controlled system with synergistic chemo-photothermal therapy has great potential capability to overcome MDR in breast cancer.

Improved Anticancer Photothermal Therapy Using the Bystander Effect Enhanced by Antiarrhythmic Peptide Conjugated Dopamine-Modified Reduced Graphene Oxide Nanocomposite.

Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO). Our AAP10-pDA/rGO could promote the bystander effect by increasing the expression of connexin 43 protein in MCF-7 breast-cancer cells. Because of its tremendous ability to absorb NIR absorption, AAP10-pDA/rGO offers a high photothermal effect under NIR irradiation. This leads to a massive death of MCF-7 cells via the bystander effect. Using tumor-bearing mice as the model, it is found that NIR radiation effectively ablates breast tumor in the presence of AAP10-pDA/rGO and inhibits tumor growth by ≈100%. Therefore, this research integrates the bystander and photothermal effects into a single nanoplatform in order to facilitate an efficient photothermal therapy. Furthermore, our AAP10-pDA/rGO, which exhibits both hyperthermia and the bystander effect, can prevent breast-cancer recurrence and, therefore, has great potential for future clinical and research applications.

Analyzing the contribution of climate change to long-term variations in sediment nitrogen sources for reservoirs/lakes.

We applied a mixing model based on stable isotopic δ(13)C, δ(15)N, and C:N ratios to estimate the contributions of multiple sources to sediment nitrogen. We also developed a conceptual model describing and analyzing the impacts of climate change on nitrogen enrichment. These two models were conducted in Miyun Reservoir to analyze the contribution of climate change to the variations in sediment nitrogen sources based on two (210)Pb and (137)Cs dated sediment cores. The results showed that during the past 50years, average contributions of soil and fertilizer, submerged macrophytes, N2-fixing phytoplankton, and non-N2-fixing phytoplankton were 40.7%, 40.3%, 11.8%, and 7.2%, respectively. In addition, total nitrogen (TN) contents in sediment showed significant increasing trends from 1960 to 2010, and sediment nitrogen of both submerged macrophytes and phytoplankton sources exhibited significant increasing trends during the past 50years. In contrast, soil and fertilizer sources showed a significant decreasing trend from 1990 to 2010. According to the changing trend of N2-fixing phytoplankton, changes of temperature and sunshine duration accounted for at least 43% of the trend in the sediment nitrogen enrichment over the past 50years. Regression analysis of the climatic factors on nitrogen sources showed that the contributions of precipitation, temperature, and sunshine duration to the variations in sediment nitrogen sources ranged from 18.5% to 60.3%. The study demonstrates that the mixing model provides a robust method for calculating the contribution of multiple nitrogen sources in sediment, and this study also suggests that N2-fixing phytoplankton could be regarded as an important response factor for assessing the impacts of climate change on nitrogen enrichment.

Photothermal therapeutic response of cancer cells to aptamer-gold nanoparticle-hybridized graphene oxide under NIR illumination.

The objective of this study was to synthesize a nanocomposite, aptamer-gold nanoparticle-hybridized graphene oxide (Apt-AuNP-GO), to facilitate targeted treatment of tumor cells by near-infrared (NIR) light-activatable photothermal therapy. We also investigated whether Apt-AuNP-GO with NIR illumination modulates heat shock proteins (HSPs) expression leading to therapeutic response in human breast cancer cells. These findings can provide strategies for improving the photothermal therapy efficacy of cancer. The self-assembled Apt-AuNP-GO nanocomposite could selectively target MUC1-positive human breast cancer cells (MCF-7) due to the specific interaction between the MUC1-binding-aptamer and the MUC1 (type I transmembrane mucin glycoprotein) on cell membrane. In addition, Apt-AuNP-GO has a high light-to-heat conversion capability for photoabsorption of NIR light, and it is able to exert therapeutic effects on MCF-7 cells at an ultralow concentration without inducing adverse effects in healthy cells. The Apt-AuNP-GO nanocomposites combine the advantages of GOs, AuNPs, and Apts, possess specific targeting capability, excellent biocompatibility, and tumor cell destruction ability, suggesting great potential for application in the photothermal therapy of breast cancer. Under NIR illumination, Apt-AuNP-GO induced transient increase in HSP70 expression, which decreased thereafter. This phenomenon may cause irreversible damage to Apt-AuNP-GO-treated MCF-7 cell under NIR illumination. We also demonstrated that the combination therapy of heat and HSP70 inhibitor could synergistically generate marked tumoricidal effects against breast cancer. These results suggest that the degree and duration of HSP70 protein expression are correlated with therapeutic effects against breast cancer for Apt-AuNP-GO-assisted photothermal therapy. We believe that such a nanocomposite can be readily extended to the construction of HSP70 inhibitors-loaded Apt-AuNP-GO, which could deliver both heat and HSP70 inhibitors to tumorigenic regions for the chemo-photothermal therapy.

The protective effects of Achyranthes bidentata polypeptides on rat sciatic nerve crush injury causes modulation of neurotrophic factors.

Pharmacological treatment is a therapeutic approach to improving nerve regeneration and functional recovery after peripheral nerve crush injury. The objective of the present study was to investigate the effects of the polypeptides isolated from Achyranthes bidentata Blume (abbreviated as ABPP) on rat sciatic crush injury and to test the possible involvement of neurotrophic factors. After surgical crush injury, rats received daily intraperitoneal injection of 0.2 ml saline containing 2 mg ABPP, 1 µg nerve growth factor (NGF) or no additive. The results from walking track analysis, electrophysiological assessment and histological evaluation indicated that the repair outcomes by ABPP treatment were close to those by NGF treatment, but better than those by treatment with saline alone. The quantitative real-time RT-PCR was used to monitor the mRNA expression of growth associated protein in the crush nerves and the mRNA expression of NGF, brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), tyrosine kinase (Trk)A and TrkB in the dorsal root ganglia (DRGs) at L4-L6. The mRNA expression of these genes in the crush nerve sample and DRGs sample was higher after treatment with ABPP or NGF than after treatment with saline alone. Our findings suggest that ABPP might protect peripheral nerve against crush injury through stimulating release of neurotrophic factors and the other cytokines.