Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport.

The biomedical use of nanoparticles (NPs) has been the focus of intense research for over a decade. As most NPs are explored as carriers to alter the biodistribution, pharmacokinetics and bioavailability of associated drugs, the delivery of these NPs to the tissues of interest remains an important topic. To date, the majority of NP delivery studies have used tumor models as their tool of interest, and the limitations concerning tumor targeting of systemically administered NPs have been well studied. In recent years, the focus has also shifted to other organs, each presenting their own unique delivery challenges to overcome. In this review, we discuss the recent advances in leveraging NPs to overcome four major biological barriers including the lung mucus, the gastrointestinal mucus, the placental barrier, and the blood-brain barrier. We define the specific properties of these biological barriers, discuss the challenges related to NP transport across them, and provide an overview of recent advances in the field. We discuss the strengths and shortcomings of different strategies to facilitate NP transport across the barriers and highlight some key findings that can stimulate further advances in this field.

Modularity of RBC hitchhiking with polymeric nanoparticles: testing the limits of non-covalent adsorption.

Red blood cell (RBC) hitchhiking has great potential in enhancing drug therapy, by improving targeting and reducing rapid clearance of nanoparticles (NPs). However, to improve the potential for clinical translation of RBC hitchhiking, a more thorough understanding of the RBC-NP interface is needed. Here, we evaluate the effects of NP surface parameters on the success and biocompatibility of NP adsorption to extracted RBCs from various species. Major differences in RBC characteristics between rabbit, mouse and human were proven to significantly impact NP adsorption outcomes. Additionally, the effects of NP design parameters, including NP hydrophobicity, zeta potential, surfactant concentration and drug encapsulation, on RBC hitchhiking are investigated. Our studies demonstrate the importance of electrostatic interactions in balancing NP adsorption success and biocompatibility. We further investigated the effect of varying the anti-coagulant used for blood storage. The results presented here offer new insights into the parameters that impact NP adsorption on RBCs that will assist researchers in experimental design choices for using RBC hitchhiking as drug delivery strategy.

LocaRDS: A Localization Reference Data Set.

The use of wireless signals for the purposes of localization enables a host of applications relating to the determination and verification of the positions of network participants ranging from radar to satellite navigation. Consequently, this has been a longstanding interest of theoretical and practical research in mobile networks and many solutions have been proposed in the scientific literature. However, it is hard to assess the performance of these in the real world and, more importantly, to compare their advantages and disadvantages in a controlled scientific manner. With this work, we attempt to improve the current state of art methodology in localization research and to place it on a solid scientific grounding for future investigations. Concretely, we developed LocaRDS, an open reference data set of real-world crowdsourced flight data featuring more than 222 million measurements from over 50 million transmissions recorded by 323 sensors. We demonstrate how we can verify the quality of LocaRDS measurements so that it can be used to test, analyze and directly compare different localization methods. Finally, we provide an example implementation for the aircraft localization problem and a discussion of possible metrics for use with LocaRDS.

Core-shell microparticles: From rational engineering to diverse applications.

Core-shell microparticles, composed of solid, liquid, or gas bubbles surrounded by a protective shell, are gaining considerable attention as intelligent and versatile carriers that show great potential in biomedical fields. In this review, an overview is given of recent developments in design and applications of biodegradable core-shell systems. Several emerging methodologies including self-assembly, gas-shearing, and coaxial electrospray are discussed and microfluidics technology is emphasized in detail. Furthermore, the characteristics of core-shell microparticles in artificial cells, drug release and cell culture applications are discussed and the superiority of these advanced multi-core microparticles for the generation of artificial cells is highlighted. Finally, the respective developing orientations and limitations inherent to these systems are addressed. It is hoped that this review can inspire researchers to propel the development of this field with new ideas.

Biomedical nanomaterials for immunological applications: ongoing research and clinical trials.

Research efforts on nanomaterial-based therapies for the treatment of autoimmune diseases and cancer have spiked and have made rapid progress over the past years. Nanomedicine has been shown to contribute significantly to overcome current therapeutic limitations, exhibiting advantages compared to conventional therapeutics, such as sustained drug release, delayed drug degradation and site-specific drug delivery. Multiple nanodrugs have reached the clinic, but translation is often hampered by either low targeting efficiency or undesired side effects. Nanomaterials, and especially inorganic nanoparticles, have gained criticism due to their potential toxic effects, including immunological alterations. However, many strategies have been attempted to improve the therapeutic efficacy of nanoparticles and exploit their unique properties for the treatment of inflammation and associated diseases. In this review, we elaborate on the immunomodulatory effects of nanomaterials, with a strong focus on the underlying mechanisms that lead to these specific immune responses. Nanomaterials to be discussed include inorganic nanoparticles such as gold, silica and silver, as well as organic nanomaterials such as polymer-, dendrimer-, liposomal- and protein-based nanoparticles. Furthermore, various approaches for tuning nanomaterials in order to enhance their efficacy and attenuate their immune stimulation or suppression, with respect to the therapeutic application, are described. Additionally, we illustrate how the acquired insights have been used to design immunotherapeutic strategies for a variety of diseases. The potential of nanomedicine-based therapeutic strategies in immunotherapy is further illustrated by an up to date overview of current clinical trials. Finally, recent efforts into enhancing immunogenic cell death through the use of nanoparticles are discussed.