To develop a pH-sensitive dual targeting magnetic nanocarrier for chemo-phototherapy in cancer treatment, we prepared magnetic graphene oxide (MGO) by depositing Fe3O4 magnetic nanoparticles on graphene oxide (GO) through chemical co-precipitation. MGO was modified with polyethylene glycol (PEG) and cetuximab (CET, an epidermal growth factor receptor (EGFR) monoclonal antibody) to obtain MGO-PEG-CET. Since EGFR was highly expressed on the tumor cell surface, MGO-PEG-CET was used for dual targeted delivery an anticancer drug doxorubicin (DOX). The physico-chemical properties of MGO-PEG-CET were fully characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, Fourier transform Infrared spectroscopy, thermogravimetric analysis, and superconducting quantum interference device. Drug loading experiments revealed that DOX adsorption followed the Langmuir isotherm with a maximal drug loading capacity of 6.35 mg/mg, while DOX release was pH-dependent with more DOX released at pH 5.5 than pH 7.4. Using quantum-dots labeled nanocarriers and confocal microscopy, intracellular uptakes of MGO-PEG-CET by high EGFR-expressing CT-26 murine colorectal cells was confirmed to be more efficient than MGO. This cellular uptake could be inhibited by pre-incubation with CET, which confirmed the receptor-mediated endocytosis of MGO-PEG-CET. Magnetic targeted killing of CT-26 was demonstrated in vitro through magnetic guidance of MGO-PEG-CET/DOX, while the photothermal effect could be confirmed in vivo and in vitro after exposure of MGO-PEG-CET to near-infrared (NIR) laser light. In addition, the biocompatibility tests indicated MGO-PEG-CET showed no cytotoxicity toward fibroblasts and elicited minimum hemolysis. In vitro cytotoxicity tests showed the half maximal inhibitory concentration (IC50) value of MGO-PEG-CET/DOX toward CT-26 cells was 1.48 µg/mL, which was lower than that of MGO-PEG/DOX (2.64 µg/mL). The IC50 value could be further reduced to 1.17 µg/mL after combining with photothermal therapy by NIR laser light exposure. Using subcutaneously implanted CT-26 cells in BALB/c mice, in vivo anti-tumor studies indicated the relative tumor volumes at day 14 were 12.1 for control (normal saline), 10.1 for DOX, 9.5 for MGO-PEG-CET/DOX, 5.8 for MGO-PEG-CET/DOX + magnet, and 0.42 for MGO-PEG-CET/DOX + magnet + laser. Therefore, the dual targeting MGO-PEG-CET/DOX could be suggested as an effective drug delivery system for anticancer therapy, which showed a 29-fold increase in therapeutic efficacy compared with control by combining chemotherapy with photothermal therapy.
The latitudinal diversity gradient (LDG) is one of the most extensive and important biodiversity patterns on the Earth. Various studies have established that species diversity increases with higher taxa numbers from the polar to the tropics. Studies of multicellular biotas have supported the LDG patterns from land (e.g., plants, animals, forests, wetlands, grasslands, fungi, and so forth) to oceans (e.g., marine organisms from freshwater invertebrates, continental shelve, open ocean, even to the deep sea invertebrates). So far, there are several hypotheses proposed to explore the diversity patterns and mechanisms of LDG, however, there has been no consensus on the underlying causes of LDG over the past few decades. Thus, we reviewed the progress of LDG studies in recent years. Although several explanations for the LDG have been proposed, these hypotheses are only based on species richness, evolution and the ecosystems. In this review, we summarize the effects of evolution and ecology on the LDG patterns to synthesize the formation mechanisms of the general biodiversity distribution patterns. These intertwined factors from ecology and evolution in the LDG are generally due to the wider distribution of tropical areas, which hinders efforts to distinguish their relative contributions. However, the mechanisms of LDG always engaged controversies, especially in such a context that the human activity and climate change has affected the biodiversity. With the development of molecular biology, more genetic/genomic data are available to facilitate the estimation of global biodiversity patterns with regard to climate, latitude, and other factors. Given that human activity and climate change have inevitably impacted on biodiversity loss, biodiversity conservation should focus on the change in LDG pattern. Using large-scale genetic/genomic data to disentangle the diversity mechanisms and patterns of LDG, will provide insights into biodiversity conservation and management measures. Future perspectives of LDG with integrative genetic/genomic, species, evolution, and ecosystem diversity patterns, as well as the mechanisms that apply to biodiversity conservation, are discussed. It is imperative to explore integrated approaches for recognizing the causes of LDG in the context of rapid loss of diversity in a changing world.
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