Differential Investment Strategies in Leaf Economic Traits Across Climate Regions Worldwide.

The leaf economics spectrum (LES) is the leading theory of plant ecological strategies based on functional traits, which explains the trade-off between dry matter investment in leaf structure and the potential rate of resource return, revealing general patterns of leaf economic traits investment for different plant growth types, functional types, or biomes. Prior work has revealed the moderating role of different environmental factors on the LES, but whether the leaf trait bivariate relationships are shifted across climate regions or across continental scales requires further verification. Here we use the Köppen-Geiger climate classification, a very widely used and robust criterion, as a basis for classifying climate regions to explore climatic differences in leaf trait relationships. We compiled five leaf economic traits from a global dataset, including leaf dry matter content (LDMC), specific leaf area (SLA), photosynthesis per unit of leaf dry mass (Amass), leaf nitrogen concentration (Nmass), and leaf phosphorus concentration (Pmass). Moreover, we primarily used the standardized major axis (SMA) analysis to establish leaf trait bivariate relationships and to explore differences in trait relationships across climate regions as well as intercontinental differences within the same climate type. Leaf trait relationships were significantly correlated across almost all subgroups (P < 0.001). However, there was no common slope among different climate zones or climate types and the slopes of the groups fluctuated sharply up and down from the global estimates. The range of variation in the SMA slope of each leaf relationship was as follows: LDMC-SLA relationships (from -0.84 to -0.41); Amass-SLA relationships (from 0.83 to 1.97); Amass-Nmass relationships (from 1.33 to 2.25); Nmass-Pmass relationships (from 0.57 to 1.02). In addition, there was significant slope heterogeneity among continents within the Steppe climate (BS) or the Temperate humid climate (Cf). The shifts of leaf trait relationships in different climate regions provide evidence for environmentally driven differential plant investment in leaf economic traits. Understanding these differences helps to better calibrate various plant-climate models and reminds us that smaller-scale studies may need to be carefully compared with global studies.

Manganese dioxide nanosheets-based redox/pH-responsive drug delivery system for cancer theranostic application.

The aim of this study was to construct redox- and pH-responsive degradable manganese dioxide (MnO2) nanosheets for cancer theranostic application. The small MnO2 nanosheets were synthesized, and then functionalized by hyaluronic acid (HA), demonstrating excellent stability and tumor-targeting ability. Cisplatin (cis-diamminedichloroplatinum [CDDP]) was absorbed by the nanosheets through a physical action, which was designed as MnO2/HA/CDDP. The prepared MnO2/HA/CDDP formulation was able to efficiently deliver CDDP to tumor cells in vitro and in vivo, resulting in improved therapeutic efficiency. Subsequently, they were triggered by lower pH and higher level of reduced glutathione to generate Mn(2+), enabling magnetic resonance imaging. The smart multifunctional system combining efficient magnetic resonance imaging and chemotherapy has the potential to be used as a tumor-targeting theranostic nanomedicine.

A gold nanostar based multi-functional tumor-targeting nanoplatform for tumor theranostic applications.

Recently, gold nanomaterials have attracted extensive attention due to their unique physical, chemical and biological properties. In this study, gold nanostars (GNSTs) were synthesized first and functionalized with polyethylene glycol (PEG) and polyethylenimine (PEI). We found that GNSTs and their derivatives can be used as radiofrequency (RF) sensitizers for hyperthermia due to their special star shaped structure. Secondly, a multi-functional tumor-targeting drug delivery system DOX/GNSTs-PEG/PEI-FA was constructed. Doxorubicin (DOX) was covalently conjugated onto GNSTs-PEG/PEI by the pH-sensitive hydrazone linkage, and folic acid (FA) was directly conjugated to excess amino groups by amidation reaction. The release profiles of DOX from GNSTs-PEG/PEI-FA showed a strong dependence on the environmental pH value. These in vitro and in vivo results revealed that this drug delivery system has FA tumor-targeting, pH-sensitive controlled release, RF induced hyperthermia and X-ray contrast imaging effects, demonstrating that DOX/GNSTs-PEG/PEI-FA can be used as a potential nano-platform for tumor theranostic applications.

Magnetic Multi-Walled Carbon Nanotubes for Tumor Theranostics.

Current diagnostic techniques do not reliably detect cancer at early stages, and traditional chemotherapy lacks specificity and causes systemic toxicity. To address these issues, multifunctional nanomaterials are becoming more widely studied as a means of cancer detection, therapy, and monitoring. Here, iron oxide (Fe3O4) nanoparticles were conjugated onto the surface of multi-walled carbon nanotubes (MWNTs), which were then modified with polyethylenimine (PEI) and polyethylene glycol (PEG) to improve their solubility and biocompatibility. Finally, human telomerase reverse transcriptase (hTERT) siRNA was loaded on the MWNT surface by electrostatic interaction to obtain a multifunctional delivery system (MWNT-Fe3O4-PEI-PEG/siRNA). This delivery system efficiently delivered siRNA, allowed targeting of certain sites by magnetic fields, facilitated photothermal heating by near infrared irradiation, and enabled magnetic resonance imaging, thereby indicating great potential for cancer theranostic applications.

Gold nanostars mediated combined photothermal and photodynamic therapy and X-ray imaging for cancer theranostic applications.

Gold nanomaterials possess unique physical and chemical properties, which attracted much attention in recent years. As a new type of gold nanomaterials, gold nanostars (GNSTs) have been prepared and characterized in this study. GNSTs under near-infrared (NIR) light irradiation can exert not only cancer photothermal therapy via heat production but also photodynamic therapy via generation of reactive oxygen species. GNSTs were able to enter the cytoplasm as well as nuclei of human breast michigan cancer foundation-7 (MCF-7) cells. Under NIR light irradiation, GNSTs caused more severe DNA damage, arrest the cell cycle in G0/G1 phase, and reduce more cellular glutathione level, causing more severe apoptosis and cell death in vitro. Intratumoral injection of GNSTs with NIR light irradiation significantly inhibited tumor growth in vivo. In addition, GNSTs were demonstrated to be a contrast agent for X-ray imaging. All the in vitro and in vivo results showed that GNSTs can be used for the potential diagnosis and medical treatment of cancer.

Targeted Imaging and Chemo-Phototherapy of Brain Cancer by a Multifunctional Drug Delivery System.

The aim of this study was to develop multifunctional poly lactide-co-glycolide (PLGA) nanoparticles with the ability to simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. ICG was selected as a near-infrared imaging and phototherapy agent and DTX was employed as a chemotherapeutic agent. ICG and DTX were simultaneously incorporated into PLGA nanoparticles with higher stability. These nanoparticles were further decorated with angiopep-2 via the outer maleimide group of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleinimide incorporated in the nanoparticles. The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/DTX/ICG nanoparticles (ANG/PLGA/DTX/ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87MG glioma xenograft-bearing mice in vivo. Thus, this study suggests that ANG/PLGA/DTX/ICG NPs have the potential for combinatorial chemotherapy and phototherapy for glioma.

Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.

It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.

Radiofrequency-triggered tumor-targeting delivery system for theranostics application.

In this study, a new type of magnetic tumor-targeting PEGylated gold nanoshell drug delivery system (DOX-TSMLs-AuNSs-PEG) based on doxorubicin-loaded thermosensitive magnetoliposomes was successfully obtained. The reverse-phase evaporation method was used to construct the magnetoliposomes, and then gold nanoshells were coated on the surface of it. The DOX-TSMLs-AuNSs-PEG delivery system was synthesized after SH-PEG2000 modification. This multifunction system was combined with a variety of functions, such as radiofrequency-triggered release, chemo-hyperthermia therapy, and dual-mode magnetic resonance/X-ray imaging. Importantly, the DOX-TSMLs-AuNSs-PEG complex was found to escape from endosomes after cellular uptake by radiofrequency-induced endosome disruption before lysosomal degradation. All results in vitro and in vivo indicated that DOX-TSMLs-AuNSs-PEG is a promising effective drug delivery system for diagnosis and treatment of tumors.