Engineered Therapeutic Plasmids and Nanoparticle Delivery Vehicles for Targeted Treatment of Hepatocellular Carcinoma

Nucleic acid-based therapies can be used to target the genetic basis of a disease and have been explored for the treatment of wide range of medical conditions, including cancer. However, many of these therapies have largely been ineffective in the clinic due to off-target toxicities and poor targeting properties, resulting in poor safety and efficacy outcomes. To address these challenges, there has been a strong effort over the past decades to develop delivery vehicles for targeted nucleic acid delivery. A high degree of targeting is particularly critical when delivering cytotoxic therapies for cancer cell killing, as off-target toxicities can lead to dangerous or deadly adverse events. In the case of liver cancer, off-target toxicity has a high risk of liver failure due to the prevalence of severe underlying liver disease in these patients. The aim of this thesis is to investigate multiple methods for targeted DNA delivery to hepatocellular carcinoma, the most common form of liver cancer. Polyplex nanoparticles (NPs) synthesized using poly(beta-amino ester) (PBAE) serve as a delivery vehicle to deliver plasmid DNA to target cells. This thesis uses PBAE NPs to explore multimodal targeting using (1) anatomical targeting of tissues, specifically HCC tumor vasculature, (2) optimization of delivery vehicle biomaterials for HCC cell-specific transfection, and (3) an HCC-specific promoter to restrict therapeutic gene expression. These methodologies are explored independently and in combination to specifically deliver DNA to HCC cells in vitro and in vivo. Importantly, these targeting principles are applied to develop two targeted therapeutics for HCC, which show therapeutic efficacy in preclinical rodent models of HCC. Altogether, these results highlight the clinical potential of PBAE NPs for targeted therapy for HCC

Micro/nanofluidic and lab-on-a-chip devices for biomedical applications

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [1]. Because of their adaptability, feasibility, and cost-efficiency, these devices can revolutionize the future of preclinical technologies. Furthermore, they allow insights into the performance and toxic effects of responsive drug delivery nanocarriers to be obtained, which consequently allow the shortcomings of two/three-dimensional static cultures and animal testing to be overcome and help to reduce drug development costs and time [2–4]. With the constant advancements in biomedical technology, the development of enhanced microfluidic devices has accelerated, and numerous models have been reported. Given the multidisciplinary of this Special Issue (SI), papers on different subjects were published making a total of 14 contributions, 10 original research papers, and 4 review papers. The review paper of Ko et al. [1] provides a comprehensive overview of the significant advancements in engineered organ-on-a-chip research in a general way while in the review presented by Kanabekova and colleagues [2], a thorough analysis of microphysiological platforms used for modeling liver diseases can be found. To get a summary of the numerical models of microfluidic organ-on-a-chip devices developed in recent years, the review presented by Carvalho et al. [5] can be read. On the other hand, Maia et al. [6] report a systematic review of the diagnosis methods developed for COVID-19, providing an overview of the advancements made since the start of the pandemic. In the following, a brief summary of the research papers published in this SI will be presented, with organs-on-a-chip, microfluidic devices for detection, and device optimization having been identified as the main topics.info:eu-repo/semantics/publishedVersio

The National Nanotechnology Initiative: Supplement to the President’s 2017 Budget

This Supplement to the President’s Budget is the annual report of the National Nanotechnology Initiative (NNI), a partnership of 20 Federal agencies and departments with activities in nanotechnology research and development (R&D), policy, and regulation. Since the inception of the NNI in 2001, participating agencies have invested nearly 24 billion (including the President’s 2017 Budget request) in fundamental and applied nanotechnology R&D; technology transfer; world-class characterization, testing, and fabrication facilities; education and workforce development; and efforts directed at understanding and controlling the environmental, health, and safety (EHS) aspects of nanotechnology. In 2015, Federal agencies invested a total of 1.5 billion in nanotechnology-related activities. The 2017 request calls for a total investment of over $1.4 billion, affirming the important role nanotechnology continues to play in the Administration’s innovation agenda. This report highlights accomplishments over the past year, discusses activities currently underway, and outlines plans for how agencies will work both in dividually and collectively in 2017 to build upon these accomplishments and further advance the goals of the NNI

Abstracts from the 50th European Society of Human Genetics Conference: Posters

International audienc