Phytoremediation of heavy metal-contaminated sites: Eco-environmental concerns, field studies, sustainability issues and future prospects

Environmental contamination due to heavy metals (HMs) is of serious ecotoxicological concern worldwide because of their increasing use at industries. Due to non-biodegradable and persistent nature, HMs cause serious soil/water pollution and severe health hazards in living beings upon exposure. HMs can be genotoxic, carcinogenic, mutagenic, and teratogenic in nature even at low concentration. They may also act as endocrine disruptors and induce developmental as well as neurological disorders and thus, their removal from our natural environment is crucial for the rehabilitation of contaminated sites. To cope with HM pollution, phytoremediation has emerged as a low-cost and eco-sustainable solution to conventional physico-chemical cleanup methods that require high capital investment and labor alter soil properties and disturb soil microflora. Phytoremediation is a green technology wherein plants and associated microbes are used to remediate HM-contaminated sites to safeguard the environment and protect public health. Hence, in view of the above, the present paper aims to examine the feasibility of phytoremediation as a sustainable remediation technology for the management of metals-contaminated sites. Therefore, this paper provides an in-depth review on both the conventional and novel phytoremediation approaches, evaluate their efficacy to remove toxic metals from our natural environment, explore current scientific progresses, field experiences and sustainability issues and revise world over trends in phytoremediation research for its wider recognition and public acceptance as a sustainable remediation technology for the management of contaminated sites in 21st century

Eruption style at Kīlauea Volcano in Hawaiʻi linked to primary melt composition

Explosive eruptions at basaltic volcanoes have been linked to gas segregation from magmas at shallow depths in the crust. The composition of primary melts formed at greater depths is thought to have little influence on eruptive style. Primary melts formed at ocean island basaltic volcanoes are probably geochemically diverse because they are often associated with melting of a heterogeneous plume source in the mantle. This heterogeneous primary melt composition, and particularly the content of volatile gases, will profoundly influence magma buoyancy, storage and eruption style. Here we analyse the geochemistry of a suite of melt inclusions from 25 historical eruptions at the ocean island volcano of K¯ılauea, Hawai’i, over the past 600 years.We find that more explosive styles of eruption at K¯ılauea Volcano are associated statistically with more geochemically enriched primary melts that have higher volatile concentrations. These enriched melts ascend faster and retain their primary nature, undergoing little interaction with the magma reservoir at the volcano’s summit. We conclude that the eruption style and magma-supply rate at K¯ılauea are fundamentally linked to the geochemistry of the primary melts formed deep below the volcano. Magmas might therefore be predisposed towards explosivity right at the point of formation in their mantle source region

Development and evaluation of a new modular nanotransporter for drug delivery into nuclei of pathological cells expressing folate receptors

Tatiana A Slastnikova,1 Andrey A Rosenkranz,1,2 Yuri V Khramtsov,1 Tatiana S Karyagina,1 Sergey A Ovechko,2 Alexander S Sobolev1,2 1Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, 2Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia Purpose: Modular nanotransporters (MNTs) are artificial multifunctional systems designed to facilitate receptor-specific transport from the cell surface into the cell nucleus through inclusion of polypeptide domains for accomplishing receptor binding and internalization, as well as sequential endosomal escape and nuclear translocation. The objective of this study was to develop a new MNT targeted at folate receptors (FRs) for precise delivery of therapeutic cargo to the nuclei of FR-positive cells and to evaluate its potential, particularly for delivery of therapeutic agents (eg, the Auger electron emitter 111In) into the nuclei of target cancer cells.Methods: A FR-targeted MNT was developed by site-specific derivatization of ligand-free MNT with maleimide-polyethylene glycol-folic acid. The ability of FR-targeted MNT to accumulate in target FR-expressing cells was evaluated using flow cytometry, and intracellular localization of this MNT was assessed using confocal laser scanning microscopy of cells. The cytotoxicity of the 111In-labeled FR-targeted MNT was evaluated on HeLa and U87MG cancer cell lines expressing FR. In vivo micro-single-photon emission computed tomography/CT imaging and antitumor efficacy studies were performed with intratumoral injection of 111In-labeled FR-targeted MNT in HeLa xenograft-bearing mice.Results: The resulting FR-targeted MNT accumulated in FR-positive HeLa cancer cell lines specifically and demonstrated the ability to reach its target destination – the cell nuclei. 111In-labeled FR-targeted MNT demonstrated efficient and specific FR-positive cancer cell eradication. A HeLa xenograft in vivo model revealed prolonged retention of 111In delivered by FR-targeted MNT and significant tumor growth delay (up to 80% growth inhibition).Conclusion: The FR-targeted MNT met expectations of its ability to deliver active cargo into the nuclei of target FR-positive cells efficiently and specifically. As a result of this finding the new FR-targeted MNT approach warrants broad evaluation. Keywords: nuclear delivery, folic acid, cancer, radionuclide therapy, indium-11

Modular nanotransporters: a versatile approach for enhancing nuclear delivery and cytotoxicity of Auger electron-emitting 125I.

UNLABELLED: BACKGROUND: This study evaluates the potential utility of a modular nanotransporter (MNT) for enhancing the nuclear delivery and cytotoxicity of the Auger electron emitter 125I in cancer cells that overexpress the epidermal growth factor receptor (EGFR). METHODS: MNTs are recombinant multifunctional polypeptides that we have developed for achieving selective delivery of short-range therapeutics into cancer cells. MNTs contain functional modules for receptor binding, internalization, endosomal escape and nuclear translocation, thereby facilitating the transport of drugs from the cell surface to the nucleus. The MNT described herein utilized EGF as the targeting ligand and was labeled with 125I using N-succinimidyl-4-guanidinomethyl-3-[125I]iodobenzoate (SGMIB). Membrane binding, intracellular and nuclear accumulation kinetics, and clonogenic survival assays were performed using the EGFR-expressing A431 epidermoid carcinoma and D247 MG glioma cell lines. RESULTS: [125I]SGMIB-MNT bound to A431 and D247 MG cells with an affinity comparable to that of native EGF. More than 60% of internalized [125I]SGMIB-MNT radioactivity accumulated in the cell nuclei after a 1-h incubation. The cytotoxic effectiveness of [125I]SGMIB-MNT compared with 125I-labeled bovine serum albumin control was enhanced by a factor of 60 for D247 MG cells and more than 1,000-fold for A431 cells, which express higher levels of EGFR. CONCLUSIONS: MNT can be utilized to deliver 125I into the nuclei of cancer cells overexpressing EGFR, significantly enhancing cytotoxicity. Further evaluation of [125I]SGMIB-MNT as a targeted radiotherapeutic for EGFR-expressing cancer cells appears warranted

Preparation, cytotoxicity, and in vivo antitumor efficacy of 111In-labeled modular nanotransporters

Tatiana A Slastnikova,1,* Andrey A Rosenkranz,1,2,* Natalia B Morozova,3 Maria S Vorontsova,3 Vasiliy M Petriev,4,5 Tatiana N Lupanova,1 Alexey V Ulasov,1 Michael R Zalutsky,6 Raisa I Yakubovskaya,3 Alexander S Sobolev1,2 1Laboratory of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, 2Department of Biophysics, Biological Faculty, Lomonosov Moscow State University, 3Department of Anticancer Therapy Modifiers and Protectors, Moscow Hertsen Research Institute of Oncology, Russian Ministry of Health Care, Moscow, 4National Medical Research Radiological Center, Russian Ministry of Health Care, Obninsk, Moscow Region, 5Department of Nuclear Medicine, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow, Russia; 6Department of Radiology, Duke University Medical Center, Durham, NC, USA *These authors contributed equally to this work Purpose: Modular nanotransporters (MNTs) are a polyfunctional platform designed to achieve receptor-specific delivery of short-range therapeutics into the cell nucleus by receptor-mediated endocytosis, endosome escape, and targeted nuclear transport. This study evaluated the potential utility of the MNT platform in tandem with Auger electron emitting 111In for cancer therapy.Methods: Three MNTs developed to target either melanocortin receptor-1 (MC1R), folate receptor (FR), or epidermal growth factor receptor (EGFR) that are overexpressed on cancer cells were modified with p-SCN-Bn-NOTA and then labeled with 111In in high specific activity. Cytotoxicity of the 111In-labeled MNTs was evaluated on cancer cell lines bearing the appropriate receptor target (FR: HeLa, SK-OV-3; EGFR: A431, U87MG.wtEGFR; and MC1R: B16-F1). In vivo micro-single-photon emission computed tomography/computed tomography imaging and antitumor efficacy studies were performed with intratumoral injection of MC1R-targeted 111In-labeled MNT in B16-F1 melanoma tumor-bearing mice.Results: The three NOTA-MNT conjugates were labeled with a specific activity of 2.7 GBq/mg with nearly 100% yield, allowing use without subsequent purification. The cytotoxicity of 111In delivered by these MNTs was greatly enhanced on receptor-expressing cancer cells compared with 111In nontargeted control. In mice with B16-F1 tumors, prolonged retention of 111In by serial imaging and significant tumor growth delay (82% growth inhibition) were found.Conclusion: The specific in vitro cytotoxicity, prolonged tumor retention, and therapeutic efficacy of MC1R-targeted 111In-NOTA–MNT suggest that this Auger electron emitting conjugate warrants further evaluation as a locally delivered radiotherapeutic, such as for ocular melanoma brachytherapy. Moreover, the high cytotoxicity observed with FR- and EGFR-targeted 111In-NOTA–MNT suggests further applications of the MNT delivery strategy should be explored. Keywords: nuclear delivery, cancer, melanoma, radionuclide therapy, Auger electron