Exploring the biological application of Penicillium fimorum-derived silver nanoparticles: In vitro physicochemical, antifungal, biofilm inhibitory, antioxidant, anticoagulant, and thrombolytic performance.

This study showed the anti-candida, biofilm inhibitory, antioxidant, anticoagulant, and thrombolytic properties of biogenic silver nanoparticles (AgNPs) fabricated by using the supernatant of Penicillium fimorum (GenBank accession number OQ568180) isolated from soil. The biogenic AgNPs were characterized by using different analytical techniques. A sharp surface plasmon resonance (SPR) peak of the colloidal AgNPs at 429.5 nm in the UV-vis spectrum confirmed the fabrication of nanosized silver particles. The broth microdilution assay confirmed the anti-candida properties of AgNPs with a minimum inhibitory concentration (MIC) of 4 µg mL-1. In the next step, the protein and DNA leakage assays as well as reactive oxygen species (ROS) assay were performed to evaluate the possible anti-candida mechanisms of AgNPs representing an increase in the total protein and DNA of supernatant along with a climb-up in ROS levels in AgNPs-treated samples. Flow cytometry also confirmed a dose-dependent cell death in the AgNPs-treated samples. Further studies also confirmed the biofilm inhibitory performance of AgNPs against Candia albicans. The AgNPs at the concentrations of MIC and 4*MIC inhibited 79.68 ± 14.38% and 83.57 ± 3.41% of biofilm formation in C. albicans, respectively. Moreover, this study showed that the intrinsic pathway may play a significant role in the anticoagulant properties of AgNPs. In addition, the AgNPs at the concentration of 500 µg mL-1, represented 49.27%, and 73.96 ± 2.59% thrombolytic and DPPH radical scavenging potential, respectively. Promising biological performance of AgNPs suggests these nanomaterials as a good candidate for biomedical and pharmaceutical applications.

Nanobiotechnological approaches in antinociceptive therapy: Animal-based evidence for analgesic nanotherapeutics of bioengineered silver and gold nanomaterials.

Pain management is a major challenge in healthcare systems worldwide. Owing to undesirable side effects of current analgesic medications, there is an exceeding need to develop the effective alternative therapeutics. Nowadays, the application of nanomaterials is being highly considered, as their exceptional properties arising from the nanoscale dimensions are undeniable. With the increasing use of metal NPs, more biocompatible and costly methods of synthesis have been developed in which different biological rescores including microorganisms, plants and algae are employed. Nanobiotechnology-based synthesis of nanosized particles is an ecological approach offering safe production of nanoparticles (NPs) by biological resources eliminating the toxicity attributed to the conventional routes. This review provides an assessment of biosynthesized silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) as antinociceptive agents in recent studies. Living animal models (mice and rats) have been used for analyzing the effect of biogenic NPs on decreasing the nociceptive pain utilizing different methods such as acetic acid-induced writhing test, hot plate test, and formalin test. Potent analgesic activity exhibited by green fabricated AgNPs and AuNPs represents the bright future of nanotechnology in the management of pain and other social and medicinal issues followed by this unpleasant sensation. Moreover, there NPs showed a protective effects on liver, kidney, and body weight in animal models that make them attractive for clinical studies. However, further research is required to fully address the harmless antinociceptive effect of NPs for clinical usage.

Nanobiotechnological approaches in anticoagulant therapy: The role of bioengineered silver and gold nanomaterials.

Nanotechnology is a novel area that has exhibited various remarkable applications, mostly in medicine and industry, due to the unique properties coming with the nanoscale size. One of the notable medical uses of nanomaterials (NMs) that attracted enormous attention recently is their significant anticoagulant activity, preventing or reducing coagulation of blood, decreasing the risk of strokes, heart attacks, and other serious conditions. Despite successful in vitro experiments, in vivo analyses are yet to be confirmed and further research is required to fully prove the safety and efficacy of nanoparticles (NPs) and to introduce them as valid alternatives to conventional ineffective anticoagulants with various shortcomings and side-effects. NMs can be synthesized through two main routes, i.e., the bottom-up route as a more preferable method, and the top-down route. In numerous studies, biological fabrication of NPs, especially metal NPs, is highly suggested given its eco-friendly approach, in which different resources can be employed such as plants, fungi, bacteria, and algae. This review discusses the green synthesis and characterization of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) as two of the most useful metal NPs, and also their alloys in different studies focussing on their anticoagulant potential. Challenges and alternative approaches to the use of these NPs as anticoagulants have also been highlighted.

Antineoplastic activity of biogenic silver and gold nanoparticles to combat leukemia: Beginning a new era in cancer theragnostic.

The American Cancer Society estimated around 61,090 new cases of leukemia were diagnosed, and around 23,660 people died from this disease in the United States alone in 2021. Due to its burden on society, there is an unmet need to explore innovative approaches to overcome leukemia. Among different strategies that have been explored, nanotechnology appears to be a promising and effective approach for therapeutics. Specifically, biogenic silver and gold nanoparticles (NPs) have attracted significant attention for their antineoplastic activity toward leukemia cancer cells due to their unique physicochemical properties. Indeed, these nanostructures have emerged as useful approaches in anti-leukemic applications, either as carriers to enhance drug bioavailability and its targeted delivery to a specific organ or as a novel therapeutic agent. This review explores recent advances in green synthesized nanomaterials and their potential use against leukemia, especially focusing on silver (Ag) and gold (Au) nanostructures. In detail, we have reviewed various eco-friendly methods of bio-synthesized NPs, their analytical properties, and toxicity effects against leukemic models. This overview confirms the satisfactory potency of biogenic NPs toward leukemic cells and desirable safety profiles against human native cells, which opens a promising door toward commercializing these types of nontherapeutic agents if challenges involve clinical validations, reproducibility, and scalability could be resolved.

Bioengineering of green-synthesized silver nanoparticles: In vitro physicochemical, antibacterial, biofilm inhibitory, anticoagulant, and antioxidant performance.

Green-synthesized nanobiomaterials can be engineered as smart nanomedicine platforms for diagnostic and therapeutic purposes in medicine. Herein, we investigated the bioengineering of silver nanoparticles (AgNPs) and evaluated their physicochemical, antibacterial, biofilm inhibitory, anticoagulant, and antioxidant performance. Characterization of the AgNPs was performed utilizing UV-visible, transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). The spherical shaped AgNPs were proven by TEM and SEM techniques. Moreover, the XRD diffraction patterns demonstrated that the nanoparticles were in a crystalline state. The DLS represented the hydrodynamic particle size of the NPs at 49.62 nm at a pH of 9. The calculated minimum inhibitory concentration (MIC) of AgNPs toward Staphylococcus aureus (ATCC 25923) was 8 µg mL-1, which was almost similar to tetracycline by the value of 4 µg mL-1. Moreover, the minimum bactericidal concentration (MBC) of AgNPs was 64 µg mL-1, which was significantly less than the determined value of 256 µg mL-1 for tetracycline. Considering the pathogenic and standard S. aureus, the evaluated concentrations of AgNPs and tetracycline showed significant biofilm inhibitory performance. Furthermore, the bioengineered AgNPs exhibited significant anticoagulant activity at 500 µg mL-1 compared to saline (P < 0.001). In addition, the biogenic AgNPs inhibited 69.73 ± 0.56% of DPPH free radicals at 500 µg mL-1, indicating considerable antioxidant potential.

Nanotechnology-based approaches for emerging and re-emerging viruses: Special emphasis on COVID-19.

In recent decades, the major concern of emerging and re-emerging viral diseases has become an increasingly important area of public health concern, and it is of significance to anticipate future pandemic that would inevitably threaten human lives. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged virus that causes mild to severe pneumonia. Coronavirus disease (COVID-19) became a very much concerned issue worldwide after its super-spread across the globe and emerging viral diseases have not got specific and reliable diagnostic and treatments. As the COVID-19 pandemic brings about a massive life-loss across the globe, there is an unmet need to discover a promising and typically effective diagnosis and treatment to prevent super-spreading and mortality from being decreased or even eliminated. This study was carried out to overview nanotechnology-based diagnostic and treatment approaches for emerging and re-emerging viruses with the current treatment of the disease and shed light on nanotechnology's remarkable potential to provide more effective treatment and prevention to a special focus on recently emerged coronavirus.

Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives.

Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer.

Cancer is one of the biggest healthcare concerns in our century, a disease whose treatment has become even more difficult following reports of drug-resistant tumors. When this happens, chemotherapy treatments fail or decrease in efficiency, leading to catastrophic consequences to the patient. This discovery, along with the fact that drug resistance limits the efficacy of current treatments, has led to a new wave of discovery for new methods of treatment. The use of nanomedicine has been widely studied in current years as a way to effectively fight drug resistance in cancer. Research in the area of cancer nanotechnology over the past decades has led to tremendous advancement in the synthesis of tailored nanoparticles with targeting ligands that can successfully attach to chemotherapy-resistant cancer by preferentially accumulating within the tumor region through means of active and passive targeting. Consequently, these approaches can reduce the off-target accumulation of their payload and lead to reduced cytotoxicity and better targeting. This review explores some categories of nanocarriers that have been used in the treatment of drug-resistant cancers, including polymeric, viral, lipid-based, metal-based, carbon-based, and magnetic nanocarriers, opening the door for an exciting field of discovery that holds tremendous promise in the treatment of these tumors.

Emerging Antineoplastic Biogenic Gold Nanomaterials for Breast Cancer Therapeutics: A Systematic Review.

Breast cancer remains as a concerning global health issue, being the second leading cause of cancer deaths among women in the United States (US) in 2019. Therefore, there is an urgent and substantial need to explore novel strategies to combat breast cancer. A potential solution may come from the use of cancer nanotechnology, an innovative field of study which investigates the potential of nanomaterials for cancer diagnosis, therapy, and theranostic applications. Consequently, the theranostic functionality of cancer nanotechnology has been gaining much attention between scientists during the past few years and is growing exponentially. The use of biosynthesized gold nanoparticles (AuNPs) has been explored as an efficient mechanism for the treatment of breast cancer. The present study supposed a global systematic review to evaluate the effectiveness of biogenic AuNPs for the treatment of breast cancer and their anticancer molecular mechanisms through in vitro studies. Online electronic databases, including Cochrane, PubMed, Scopus, Web of Science, Science Direct, ProQuest, and Embase, were searched for the articles published up to July 16, 2019. Our findings revealed that plant-mediated synthesis was the most common approach for the generation of AuNPs. Most of the studies reported spherical or nearly spherical-shaped AuNPs with a mean diameter less than 100 nm in size. A significantly larger cytotoxicity was observed when the biogenic AuNPs were tested towards breast cancer cells compared to healthy cells. Moreover, biogenic AuNPs demonstrated significant synergistic activity in combination with other anticancer drugs through in vitro studies. Although we provided strong and comprehensive preliminary in vitro data, further in vivo investigations are required to show the reliability and efficacy of these NPs in animal models.

Genotoxicity assessment of carbon-based nanomaterials; Have their unique physicochemical properties made them double-edged swords?

Carbon-based nanomaterials (CNMs) have attracted a great deal of attention because of their outstanding combinations of physicochemical properties. The unique physicochemical properties of CNMs have made them promising nanomaterials (NMs) for a large number of applications. However, these size-dependent properties serve as a double-edged sword, which makes them fascinating materials with specific features. In particular, some health hazards have been associated with exposure to NMs. Among these hazards, genotoxicity has been the subject of intense research due to its role in inducing cancer-causing inheritable mutations. High reactivity, agglomeration tendency, and a high surface-to-volume ratio of CNMs make their interactions with biological moieties unknown, complicated, and multifactorial-dependent. In this regard, the genotoxicity of each part of the CNMs family must be evaluated and considered together with other parameters. Because of the increasing application of CNMs in everyday goods and products, as well as the growth in the potential exposure of humans to CNMs, there is a critical need to assess the genotoxic potential of each part of the CNMs family. Therefore, the main objective of this review is to provide an overview of the potential genotoxicity of CNMs and explore risk assessment strategies to quickly screen and assess emerging CNMs. It is critical to pay equal attention to both nongenotoxic and genotoxic CNMs, because some CNMs identified as nongenotoxic NMs may promote or aid the progression of the tumors.

Green Nanotechnology-based Gold Nanomaterials for Hepatic Cancer Therapeutics: A Systematic Review.

The objective of the current study was to systematically review the in-vitro anticancer activity of green synthesized gold nanoparticles (AuNPs) against hepatic cancer cells. The articles were identified through electronic databases, including PubMed, Scopus, Embase, Web of Science, Science Direct, ProQuest, and Cochrane. In total, 20 articles were found eligible to enter into our systematic review. Our findings showed that 65% of the articles used herbal extracts for the synthesis of AuNPs. Significantly, almost all of the articles stated the biofabrication of AuNPs below 100 nm in diameter. Impressively, most of the studies showed significant anticancer activity against HepG2 cells. Molecular studies stated the induction of apoptosis through the AuNPs-treated cells. We provided valuable information about the molecular mechanisms of AuNPs-induced cytotoxicity against HepG2 cells as well as their biocompatibility. The studies represented that AuNPs can be effective as anticancer drug nanocarrier for drug delivery systems. In addition, AuNP surface functionalization provides an opportunity to design multifunctional nanoparticles by conjugating them to diagnostic and/or therapeutic agents for theranostic purposes. Overall, our findings depicted considerable biogenic AuNPs-induced cytotoxicity, however, future studies should assess the anticancer activity of biogenic AuNPs through in-vivo studies, which was missing from such studies.

Redox interactions and genotoxicity of metal-based nanoparticles: A comprehensive review.

Nanotechnology is a growing science that may provide several new applications for medicine, food preservation, diagnostic technologies, and sanitation. Despite its beneficial applications, there are several questions related to the safety of nanomaterials for human use. The development of nanotechnology is associated with some concerns because of the increased risk of carcinogenesis following exposure to nanomaterials. The increased levels of reactive oxygen species (ROS) that are due to exposure to nanoparticles (NPs) are primarily responsible for the genotoxicity of metal NPs. Not all, but most metal NPs are able to directly produce free radicals through the release of metal ions and through interactions with water molecules. Furthermore, the increased production of free radicals and the cell death caused by metal NPs can stimulate reduction/oxidation (redox) reactions, leading to the continuous endogenous production of ROS in a positive feedback loop. The overexpression of inflammatory mediators, such as NF-kB and STATs, the mitochondrial malfunction and the increased intracellular calcium levels mediate the chronic oxidative stress that occurs after exposure to metal NPs. In this paper, we review the genotoxicity of different types of metal NPs and the redox mechanisms that amplify the toxicity of these NPs.

A Systematic Review of the Genotoxicity and Antigenotoxicity of Biologically Synthesized Metallic Nanomaterials: Are Green Nanoparticles Safe Enough for Clinical Marketing?

Background and objectives: Although studies have elucidated the significant biomedical potential of biogenic metallic nanoparticles (MNPs), it is very important to explore the hazards associated with the use of biogenic MNPs. Evidence indicates that genetic toxicity causes mutation, carcinogenesis, and cell death. Materials and Methods: Therefore, we systematically review original studies that investigated the genotoxic effect of biologically synthesized MNPs via in vitro and in vivo models. Articles were systematically collected by screening the literature published online in the following databases; Cochrane, Web of Science, PubMed, Scopus, Science Direct, ProQuest, and EBSCO. Results: Most of the studies were carried out on the MCF-7 cancer cell line and phytosynthesis was the general approach to MNP preparation in all studies. Fungi were the second most predominant resource applied for MNP synthesis. A total of 80.57% of the studies synthesized biogenic MNPs with sizes below 50 nm. The genotoxicity of Ag, Au, ZnO, TiO2, Se, Cu, Pt, Zn, Ag-Au, CdS, Fe3O4, Tb2O3, and Si-Ag NPs was evaluated. AgNPs, prepared in 68.79% of studies, and AuNPs, prepared in 12.76%, were the two most predominant biogenic MNPs synthesized and evaluated in the included articles. Conclusions: Although several studies reported the antigenotoxic influence of biogenic MNPs, most of them reported biogenic MNP genotoxicity at specific concentrations and with a dose or time dependence. To the best of our knowledge, this is the first study to systematically evaluate the genotoxicity of biologically synthesized MNPs and provide a valuable summary of genotoxicity data. In conclusion, our study implied that the genotoxicity of biologically synthesized MNPs varies case-by-case and highly dependent on the synthesis parameters, biological source, applied assay, etc. The gathered data are required for the translation of these nanoproducts from research laboratories to the clinical market.

Nanobiotechnology as an emerging approach to combat malaria: A systematic review.

Mosquitoes (Diptera; Culicidae) present a major threat to millions of people and animals worldwide, as they act as vectors for various pathogens, especially parasites and viruses. Resistance to insecticides, such as organophosphates and microbial control agents, and insufficient adherence to application guidelines are common reasons for insecticide treatment failure. Therefore, there is an urgent need for exploration of safer, cheaper, and more effective agents, with novel modes of action, to improve mosquito control. Biosynthesized nanoparticles (NPs) have recently been considered as a potential approach for combating vectors of malaria and also as a treatment for malaria. Here, we present current knowledge about the characterization and effectiveness of biogenic NPs against major vectors of malaria, including avian malaria (which may also provide useful insights on vectors of human malaria). This article is the first systematic review of the effects of biosynthesized nanoparticles on both malaria parasites (Plasmodium spp.) and relevant vectors.

Fungus-mediated Extracellular Biosynthesis and Characterization of Zirconium Nanoparticles Using Standard Penicillium Species and Their Preliminary Bactericidal Potential: A Novel Biological Approach to Nanoparticle Synthesis.

Biological synthesis of nanoparticles (NPs) has gained extensive attention during recent years by using various biological resources such as plant extracts and microorganisms as reducing and stabilizing agents. The objective of the present study was to biosynthesize zirconium NPs using Penicillium species as a reliable and eco-friendly protocol for the first time. The synthesized NPs were characterized using Scanning Electron Microscope (SEM), Atomic Force Microscope (AFM), Dynamic Light Scattering (DLS), Energy Dispersive X-ray (EDX), and Fourier Transform Infrared (FT-IR). The results showed that three Penicillium species were able to synthesize zirconium NPs extracellularly with spherical morphology below 100 nm. Moreover, the preliminary antibacterial activity of zirconium NPs represented considerable antibacterial potential against Gram-negative bacteria. Overall, the current study demonstrated a novel bio-based approach for preparation of zirconium NPs. Further studies are required to expend this laboratory-based investigation to an industrial scale owing to their superiorities over traditional physicochemical methods such as cost-effectiveness and eco-friendliness.

Efficacy of green nanoparticles against cancerous and normal cell lines: a systematic review and meta-analysis.

This study aimed to perform a systematic review and meta-analysis of papers discussing the efficacy of microbial synthesised metallic nanoparticles (MNPs) against cancerous and normal cell lines by exploiting Bayesian generalised linear (BGL) model. Data was systematically collected from published papers via Cochrane library, Web of Science, PubMed, Science Direct, ProQuest, Scopus, and Embase. Impressively, most of the studies were carried out on HeLa and A549 cancer cell lines. Specifically, a hefty 65.67% of studies employed bacteria to biofabricate MNPs. Significantly, BGL meta-analysis represented highly valuable information. Hence, based on adjusted analysis, the MNPs with the size of 25-50 nm were found to be far less cytotoxic than the MNPs with the size of ≤25 nm (OR = 0.233, P ˂ 0.05) against either cancerous or normal cell lines. Interestingly, it was found that the odds of cytotoxicity in cancerous cell lines were practically nine times more than normal cell lines, representing the substantially more cytotoxicity of MNPs in cancerous cell lines (OR = 9.004, P ˂ 0.001). Green MNPs mentioned here may be developed as novel anti-cancer agents, which could lead to a revolution in the treatment of cancer.

Nano-Medicine as a Newly Emerging Approach to Combat Human Immunodeficiency Virus (HIV).

BACKGROUND: Human Immuno deficiency Virus (HIV) infection has attained pandemic level due to its complexity on both the HIV infection cycle and on the targets for drug delivery. This limits medication and consequently requires prominent and promising drug delivery systems to be invented. Notably, various nanomaterial have been studied to enhance effective delivery of the antiretroviral drugs for HIV prevention, diagnosis and cure. Some of these nanomaterials are liposomes, dendrimers, inorganic nanoparticles (NPs), polymeric micelles, natural and synthetic polymers. OBJECTIVE: The present study aimed to review the recent progress in nanomedicine as a newly emerging approach to combat HIV. METHODS: The scientific data bases reviewed carefully to find both in vitro and in vivo studies representing the role of nonomedicine to combat HIV. RESULTS: Impressively, nanomedicine drug delivery systems have been commendable in various models ranging from in vitro to in vivo. It gives notion about the application of nano-carrier systems for the delivery of anti-retroviral drugs which ideally should provide better distribution to surpass Blood- Brain Barrier (BBB) and other tissue or to overcome innate barriers such as mucus. Considerably, nanomaterials such as dendrimers and many other inorganic NPs such as silver, gold, iron, and zinc can be used for HIV treatment by interfering in varying stages of HIV life cycle. Furthermore, NPs could best act as adjuvants, convoys during vaccine delivery, as intra-vaginal microbicides and for the early detection of HIV-1 p24 antigen. CONCLUSION: Nanomedicine may be a proper approach in HIV/AIDS therapy by means of offering lower dosage and side effect, better patient-to-patient consistency, bioavailability, target specificity and improved sensitivity of HIV diagnosis.

Biosynthesis and Characterization of Biogenic Tellurium Nanoparticles by Using Penicillium chrysogenum PTCC 5031: A Novel Approach in Gold Biotechnology.

Production of nanoparticles has been attractive by biological based fabrication as an alternative to physical and chemical approaches due to exceeding need to develop safe, reliable, clean and eco-friendly methods for the preparation of nanoparticle for pharmaceutical and biomedical applications. In the present study, biogenic tellurium nanoparticles (TeNPs) were successfully prepared using potassium tellurite (K2TeO3, 3H2O) via an eco-friendly and simple green approach by exploiting extracellular enzymes and biomolecules secreted from Penicillium chrysogenum PTCC 5031 at room temperature for the first time. The biofabricated TeNPs were characterized by Atomic Force Microscope (AFM), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Energy Dispersive X-ray spectroscopy (EDX), and Fourier Transform Infrared (FT-IR) spectrum. The AFM and SEM images revealed that the TeNPs were fairly uniform in size with a spherical shape and superior monodispersity. Furthermore, the DLS indicated that the average hydrodynamic diameter of TeNPs was around 50.16 nm and polydispersity index (PdI) of 0.012. The EDX results depicted that TeNPs display an absorption peak at 3.8 keV, indicating the presence of the elemental tellurium. Additionally, the FT-IR analysis of TeNPs exhibited the presence of possible functional groups that may have a role as bioreducers and capping agents. Overall, the results strongly suggested that P. chrysogenum can be a potential nanofactory for the preparation of TeNPs due to several advantages including non-pathogenic organism, fast growth rate, and high capacity of elemental ions reduction, as well as facile and economical biomass handling.