Lessons from Theranos - Restructuring Biomedical Innovation.

After raising more than $700 million, Elizabeth Holmes, the founder and chief executive officer of a healthcare startup once valued at $10 billion, was found guilty on four charges of defrauding investors. Founded in 2003, Theranos Inc. was a privately held corporation that aimed to disrupt the diagnostics industry with rapid, direct-to-consumer laboratory testing using only "a drop of blood" and the company's patented Nanotainer technology. By exploiting gaps in regulatory policy, Theranos brought its panel of laboratory tests to patients without pre-market review or validation from peer-reviewed scientific research. Investigations into Theranos' dubious operations and inaccurate test results exposed the failed venture which had squandered millions of dollars. Theranos affected the lives and health of patients further disrupting an already tenuous relationship between healthcare and the public - the importance of which cannot be understated in the setting of the COVID-19 pandemic. As medical systems address a national public health crisis and pervasive structural inequities, we must align stakeholder incentives between industry and academic biomedical innovation to rebuild trust with our patients.

Safe- and sustainable-by-design: The case of Smart Nanomaterials. A perspective based on a European workshop.

The European Commission's Green Deal is a major policy initiative aiming to achieve a climate-neutral, zero-pollution, sustainable, circular and inclusive economy, driving both the New Industrial Strategy for Europe and the Chemicals Strategy for Sustainability. Innovative materials can help to reach these policy goals, but they need to be safe and sustainable themselves. Thus, one aim is to shift the development of chemicals to Safe- and Sustainable-by-Design, and define a new systems approach and criteria for sustainability to achieve this. An online workshop was organised in September 2020 by the Joint Research Centre and the Directorate-General Research and Innovation of the European Commission, with participants from academia, non-governmental organisations, industry and regulatory bodies. The aims were to introduce the concept of Safe- and Sustainable-by-Design, to identify industrial and regulatory challenges in achieving safer and more sustainable Smart Nanomaterials as an example of innovative materials, and to deliver recommendations for directions and actions necessary to meet these challenges. The following needs were identified: (i) an agreed terminology, (ii) a common understanding of the principles of Safe- and Sustainable-by-Design, iii) criteria, assessment tools and incentives to achieve a transition from Safe-by-Design to Safe- and Sustainable-by-Design, and (iv) preparedness of regulators and legislation for innovative chemicals/nanomaterials. This paper presents the authors' view on the state of the art as well as the needs for future activities, based on discussions at the workshop and further considerations. The case of Smart Nanomaterials is used to illustrate the Safe- and Sustainable-by-Design concept and challenges for its implementation. Most of the considerations can be extended to other advanced materials and to chemicals and products in general.

Quality by design tools reducing the gap from bench to bedside for nanomedicine.

Pharmaceutical nanotechnology research is focused on smart nano-vehicles, which can deliver active pharmaceutical ingredients to enhance their efficacy through any route of administration and in the most varied therapeutical application. The design and development of new nanopharmaceuticals can be very laborious. In recent years, the application of mathematics, statistics and computational tools is emerging as a convenient strategy for this purpose. The application of Quality by Design (QbD) tools has been introduced to guarantee quality for pharmaceutical products and improve translational research from the laboratory bench into applicable therapeutics. In this review, a collection of basic-concept, historical overview and application of QbD in nanomedicine are discussed. A specific focus has been put on Response Surface Methodology and Artificial Neural Network approaches in general terms and their application in the development of nanomedicine to monitor the process parameters obtaining optimized system ensuring its quality profile.

Graphene oxide assisted light-up aptamer selection against Thioflavin T for label-free detection of microRNA.

We selected an aptamer against a fluorogenic dye called Thioflavin T (ThT). Aptamers are single-stranded DNA that can bind a specific target. We selected the ThT aptamer using graphene oxide assisted SELEX and a low-cost Open qPCR instrument. We optimized, minimized, and characterized the best aptamer candidate against ThT. The aptamer, ThT dye, and the enzymatic strand displacement amplification (SDA) were used in a label-free approach to detect the micro RNA miR-215 in saliva and serum. The aptamer confers higher specificity than intercalating dyes but without expensive covalently modified DNA probes. This isothermal, low-cost, simple method can detect both DNA and RNA. The target, miR-215, was detected with a limit of detection of 2.6 nM.

Understanding the influence of experimental factors on bio-interactions of nanoparticles: Towards improving correlation between in vitro and in vivo studies.

Bionanotechnology has developed rapidly over the past two decades, owing to the extensive and versatile, functionalities and applicability of nanoparticles (NPs). Fifty-one nanomedicines have been approved by FDA since 1995, out of the many NPs based formulations developed to date. The general conformation of NPs consists of a core with ligands coating their surface, that stabilizes them and provides them with added functionalities. The physicochemical properties, especially the surface composition of NPs influence their bio-interactions to a large extent. This review discusses recent studies that help understand the nano-bio interactions of iron oxide and gold NPs with different surface compositions. We discuss the influence of the experimental factors on the outcome of the studies and, thus, the importance of standardization in the field of nanotechnology. Recent studies suggest that with careful selection of experimental parameters, it is possible to improve the positive correlation between in vitro and in vivo studies. This provides a fundamental understanding of the NPs which helps in assessing their potential toxic side effects and may aid in manipulating them further to improve their biocompatibility and biosafety.

Nanocharacterization, Materials Modeling, and Research Integrity as Enablers of Sound Risk Assessment: Designing Responsible Nanotechnology.

Nanotechnology, as a mature enabling technology, has great potential to boost societal welfare. However, nanomaterials' current and foreseen applications raise serious concerns about their impact on human health and the environment. These concerns emerge because a reliable risk assessment in nanotechnology is yet to be achieved. The reasons for such a shortcoming are the inherent difficulties in characterizing nanomaterials properties. The interaction of characterization with modeling is an open issue and, due to overarching concerns about the reliability of research results, usually framed within the context of research integrity. This essay explores the connection between these different, but deeply intertwined concerns and the way they enable the production of responsible nanotechnology, i.e., nanotechnology devoted to societal welfare.

Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials.

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally.

Drug Nanocrystals: A Comprehensive Review with Current Regulatory Guidelines.

Drug nanocrystals offer an attractive approach for improving the solubility and dissolution rate of poorly soluble drugs which accounts for nearly 40 % newly discovered drug molecules. Both methods for manufacturing drug nanocrystals have high industrial acceptability for being simple and easy to scale which is evident from the number of approved products available in the market. Ability to modify multiple aspects of dosage form like bioavailability, release pattern and dosage form requirement along with flexibility in choosing final dosage form starting from the tablet, capsule, suspension to parenteral one, have made nanocrystal technology one of the very promising and adaptable technology for dosage form design.

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics.

BACKGROUND: The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. OBJECTIVE: The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. METHODS: In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via; the loading of various anticancer agents. RESULTS: Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via; the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. CONCLUSION: CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

Nano-biosensor for the in vitro lactate detection using bi-functionalized conducting polymer/N, S-doped carbon; the effect of αCHC inhibitor on lactate level in cancer cell lines.

A robust amperometric sensor was developed for the lactate detection in the extracellular matrix of cancer cells. The sensor was fabricated by separately immobilizing nicotinamide adenine dinucleotide (NAD+) onto a carboxylic acid group and lactate dehydrogenase (LDH) onto an amine group of bi-functionalized conducting polymer (poly 3-(((2,2':5',2″-terthiophen)-3'-yl)-5-aminobenzoic acid (pTTABA)) composited with N, S-doped porous carbon. Morphological features of the composite layer and sensor performance were investigated using FE-SEM, XPS, and electrochemical methods. The experimental parameters were optimized to get the best results. The calibration plot showed a linear dynamic range between 0.5 µM and 4.0 mM with the detection limit of 112 ± 0.02 nM. The proposed sensor was applied to detect lactate in a non-cancerous (Vero) and two cancer (MCF-7 and HeLa) cell lines. Among these cell lines, MCF-7 was mostly affected by the administration of lactate transport inhibitor, α-cyano-4-hydroxycinnamate (αCHC), followed by HeLa and Vero, respectively. Furthermore, the effect of αCHC concentration and treatment time on the lactate level in the cell lines were demonstrated. Finally, cytotoxicity studies were also performed to evaluate the effect of αCHC on cell viability.

Emerging Standards and Analytical Science for Nanoenabled Medical Products.

Development and application of nanotechnology-enabled medical products, including drugs, devices, and in vitro diagnostics, are rapidly expanding in the global marketplace. In this review, the focus is on providing the reader with an introduction to the landscape of commercially available nanotechnology-enabled medical products as well as an overview of the international documentary standards and reference materials that support and facilitate efficient regulatory evaluation and reliable manufacturing of this diverse group of medical products. We describe the materials, test methods, and standards development needs for emerging medical products. Scientific and measurement challenges involved in the development and application of innovative nanoenabled medical products motivate discussion throughout this review.

Stumbling through the Research Wilderness, Standard Methods To Shine Light on Electrically Conductive Nanocomposites for Future Healthcare Monitoring.

Electrically conductive nanocomposites are an exciting ever-expanding area of research that has yielded many versatile technologies for wearable health devices. Acting as strain-sensing materials, real-time medical diagnostic tools based on these materials may very well lead to a golden age of healthcare. Currently, the goal in research is to create a material that simultaneously has both a large gauge factor (G) and sensing range. However, a weakness in the area of electromechanical research is the lack of standardization in the reporting of the figure of merit (i.e., G) and the need for other intrinsic metrics to give researchers a more complete view of the research landscape of resistive-type sensors. A paradigm shift in the way in which data are reported is required, to push research in the right direction and to facilitate achieving research goals. Here, we report a standardized method for reporting strain-sensing performance and the introduction of the working factor (W) and the Young's modulus (Y) of a material as figures of merit for sensing materials. Using this standard method, we can define the benchmarks for an optimum sensing material (G > 7, W > 1, Y < 300 kPa) using limits set by standard commercial materials and the human body. Using extrapolated data from 200 publications normalized to this standard method, we can review what composite types meet these benchmark limits, what governs composite performances, the literary trends in composites, and the future prospects of research.

Opportunities and challenging issues of nanomaterials in otological fields: an occupational health perspective.

Nanotechnology may offer innovative solutions to overcome the physiological and anatomical barriers that make the diagnosis and treatment of ear diseases an extremely challenging issue. However, despite the solutions provided by nano-applications, the still little-known toxicological behavior of nanomaterials raised scientific concerns regarding their biosafety for treated patients and exposed workers. Therefore, this review provides an overview on recent developments and upcoming opportunities in nanoscale otological applications, and critically assesses possible adverse effects of nanosized compounds on ear structures and hearing functionality. Although such preliminary data do not allow to draw definite strategies for the evaluation of nanomaterial ototoxicity, they can still be useful to improve scientific community and workforce awareness regarding possible nanomaterial adverse effects on ear.

A One Health approach to managing the applications and implications of nanotechnologies in agriculture.

The need for appropriate science and regulation to underpin nanosafety is greater than ever as ongoing advances in nanotechnology are rapidly translated into new industrial applications and nano-enabled commercial products. Nevertheless, a disconnect persists between those examining risks to human and environmental health from nanomaterials. This disconnect is not atypical in research and risk assessment and has been perpetuated in the case of engineered nanomaterials by the relatively limited overlap in human and environmental exposure pathways. The advent of agri-nanotechnologies brings both increased need and opportunity to change this status quo as it introduces significant issues of intersectionality that cannot adequately be addressed by current discipline-specific approaches alone. Here, focusing on the specific case of nanoparticles, we propose that a transdisciplinary approach, underpinned by the One Health concept, is needed to support the sustainable development of these technologies.

Sustainability criteria for assessing nanotechnology applicability in industrial wastewater treatment: Current status and future outlook.

Application of engineered nanomaterials for the treatment of industrial effluents and to deal with recalcitrant pollutants has been noticeably promoted in recent years. Laboratory, pilot and full-scale studies emphasize the potential of this technology to offer promising treatment options to meet the future needs for clean water resources and to comply with stringent environmental regulations. The technology is now in the stage of being transferred to the real applications. Therefore, the assessment of its performance according to sustainability criteria and their incorporation into the decision-making process is a key task to ensure that long term benefits are achieved from the nano-treatment technologies. In this study, the importance of sustainability criteria for the conventional and novel technologies for the treatment of industrial effluents was determined in a general approach assisted by a fuzzy-Delphi method. The criteria were categorized in technical, economic, environmental and social branches and the current situation of the nanotechnology regarding the criteria was critically discussed. The results indicate that the efficiency and safety are the most important parameters to make sustainable choices for the treatment of industrial effluents. Also, in addition to the need for scaling-up the nanotechnology in various stages, the study on their environmental footprint must continue in deeper scales under expected environmental conditions, in particular the synthesis of engineered nanomaterials and the development of reactors with the ability of recovery and reuse the nanomaterials. This paper will aid to select the most sustainable types of nanomaterials for the real applications and to guide the future studies in this field.

Prospects, challenges and need for regulation of nanotechnology with special reference to India.

To meet the challenges of food security in a sustainable way, technological intervention in agriculture is of prime importance. With the existing conventional technologies supporting high yield, better crop production and protection, the emphasis is now on use of nanotechnology. Exploring new applications of nanotechnology has gained momentum in recent years and has shown acceptance in sectors like food, medicine, chemistry etc. As compared to other sectors, the accepted role in agriculture can still be considered on the marginal side in terms of nanotechnology application. Nanotechnology offers a potential to open large scope of novel application in the fields of biotechnology and agricultural industries due to unique physicochemical properties. Nanoparticles can be used in herbicides, nano-pesticide, nano-fertilizers, or genes, which target specific cellular organelles in plant to release their content. It can potentially play an instrumental role in minimizing the application losses of agrochemicals due to their more stable emulsion, higher coverage on leaf surface, precision application, etc. Understanding that the conventional and macro-technologies in agriculture do not ensure sustainable food security and environmentally safe methods; the researchers are now inclined for more précised nanotechnology based applications. There is still a huge untapped potential of nanomaterials to be used a future technology in agriculture which remains to be explored. Besides offering potential benefits, there are high concerns about the potential challenges associated with nanoparticles. To address the safety concerns about nanoparticles, it is important that a strong regulation system should be developed. Presently, very few countries have started focusing on keeping nanoregulation on their agenda. It is very important for agricultural and biodiverse country like India to set up norms of use nanoregulation and bring nanotechnology on the safe technology net.

The Overview of Methods of Nanoparticle Exposure Assessment.

Nanotechnology is now widely used in industry as well as consumer products, such as electrical devices, cosmetics, medicine, and household appliances. In the life cycle of the nano-products, including production, use, and disposal, nanoparticles may be released to the environment. However, there is no current consensus on the best method for evaluating and characterizing nanoparticle exposure. Therefore, this chapter focuses on the nanoparticle exposure assessment methods and sampling techniques.

Nanotechnology in Plants.

The integration of nanotechnology in medicine has had a tremendous impact in the past few decades. The discovery of synthesis of nanomaterials (NMs) and their functions as versatile tools promoted various applications in nano-biotechnology and nanomedicine. Although the physical and chemical methods are still considered as commonly used methods, they introduce several drawbacks such as the use of toxic chemicals (solvent, reducing, and capping agents) and poor control of size, size distribution, and morphology, respectively. Additionally, the NMs synthesized in organic solvents and hydrophobic surfactants rapidly aggregate in aqueous solutions or under physiologic conditions, limiting their applications in medicine. Many of the phase-transfer strategies were developed and applied for the transfer of NMs into aqueous solutions. Although great efforts have been put into phase transfers, they mostly include expensive, time-consuming, intensive labor work, multi steps, and complicated procedures.Use of plant extracts in the biological synthesis method offers stark advantages over other biomolecules (protein, enzyme, peptide, and DNA). Plant extracts have been commonly used for food, medicine, NM synthesis, and biosensing. There are many viable techniques developed for the production of plant extracts with various contents based on their simplicity, cost, and the type of extract content. In this chapter, we conduct a comparative study for extract preparation techniques, the use of extracts for metallic single and hybrid nanoparticle (NP) synthesis, and their antimicrobial properties against pathogenic and plant-based bacteria. Graphical Abstract.

Characterization and analytical development for amphiphilic poly(γ-glutamic acid) as raw material of nanoparticle adjuvants.

Amphiphilic graft copolymer consisting of poly(γ-glutamic acid) (γ-PGA) as the hydrophilic backbone and L-phenylalanine ethyl ester (Phe) as the hydrophobic side chain is an important biodegradable polymer with great potential in medical applications. In this research, we established analytical methods for the characterization and quality control of γ-PGA-graft-Phe (γ-PGA-Phe), which forms nanoparticles in aqueous solution, as a deployment platform in practical applications for vaccine adjuvants. The SEC-RI/MALS system, which uses size exclusion chromatography (SEC) coupled with a multi_angle light scattering (MALS) detector and refractive index (RI) detector, was developed to evaluate the characteristics of various types of polymers. By this method, it was indicated that absolute molecular weight (MW) should be used to measure the branch polymer. A gradient reversed phase HPLC (RP-HPLC) method was developed for the content of γ-PGA-Phe and the impurity levels to control product quality and safety. This quantitative approach could become key elements for identifying and characterizing γ-PGA-Phe. In addition, the degradation mechanism of γ-PGA-Phe was also identified as cleavage of main-chain of γ-PGA-Phe based on the stability study of γ-PGA-Phe in buffer solution with various pH values. The analytical developments described above will be important for use in both characterization and formulation design of biopolymers. Nanoparticles (NPs) composed of well-characterized biodegradable γ-PGA-Phe are expected to have a variety of potential clinical applications such as their use as drug and vaccine carriers.