Physical stimuli-responsive vesicles in drug delivery: Beyond liposomes and polymersomes

Over the past few decades, a range of vesicle-based drug delivery systems have entered clinical practice and several others are in various stages of clinical translation. While most of these vesicle constructs are lipid-based (liposomes), or polymer-based (polymersomes), recently new classes of vesicles have emerged that defy easy classification. Examples include assemblies with small molecule amphiphiles, biologically derived membranes, hybrid vesicles with two or more classes of amphiphiles, or more complex hierarchical structures such as vesicles incorporating gas bubbles or nanoparticulates in the lumen or membrane. In this review, we explore these recent advances and emerging trends at the edge and just beyond the research fields of conventional liposomes and polymersomes. A focus of this review is the distinct behaviors observed for these classes of vesicles when exposed to physical stimuli - such as ultrasound, heat, light and mechanical triggers - and we discuss the resulting potential for new types of drug delivery, with a special emphasis on current challenges and opportunities

Revisiting cell-particle association in vitro: A quantitative method to compare particle performance

Nanoengineering has the potential to revolutionize medicine by designing drug delivery systems that are both efficacious and highly selective. Determination of the affinity between cell lines and nanoparticles is thus of central importance, both to enable comparison of particles and to facilitate prediction of in vivo response. Attempts to compare particle performance can be dominated by experimental artifacts (including settling effects) or variability in experimental protocol. Instead, qualitative methods are generally used, limiting the reusability of many studies. Herein, we introduce a mathematical model-based approach to quantify the affinity between a cell-particle pairing, independent of the aforementioned confounding artifacts. The analysis presented can serve as a quantitative metric of the stealth, fouling, and targeting performance of nanoengineered particles in vitro. We validate this approach using a newly created in vitro dataset, consisting of seven different disulfide-stabilized poly(methacrylic acid) particles ranging from ~100 to 1000 nm in diameter that were incubated with three different cell lines (HeLa, THP-1, and RAW 264.7). We further expanded this dataset through the inclusion of previously published data and use it to determine which of five mathematical models best describe cell-particle association. We subsequently use this model to perform a quantitative comparison of cell-particle association for cell-particle pairings in our dataset. This analysis reveals a more complex cell-particle association relationship than a simplistic interpretation of the data, which erroneously assigns high affinity for all cell lines examined to large particles. Finally, we provide an online tool (http://bionano.xyz/estimator), which allows other researchers to easily apply this modeling approach to their experimental results

Towards Responsible Research Career Assessment

Contact: [email protected] Policy brief Growing evidence suggests that the evaluation of researchers’ careers on the basis of narrow definitions of excellence is restricting diversity in academia, both in the development of its labour force and its approaches to address societal challenges. The current research evaluation system is hampering diverse career pathways spanning research, teaching and (community) service. It inhibits the inclusion and retention of minorities, women, people from lower socio-economic backgrounds and meaningful public engagement with research. Improving the evaluation system in a concerted effort with research institutes and other funders will help fully realize a European Research Area (ERA) that is open to all talents. This diversity is essential to sustain academic careers, to strengthen the relevance and impact of science for society, and to enhance the resilience of our society and environment. Advice to MSCA policymakers Increasing attention to responsibility in, of and for research practices (as evidenced in Responsible Research and Innovation and Open Science in the ERA), has galvanized researchers and organisations to call for a change in the research evaluation system. While the academic evaluation landscape is shifting (as documented in the following pages), much remains to be done. The Marie Skłodowska-Curie Actions (MSCA) can spearhead these developments by implementing the following recommendations: Broaden current evaluation criteria of MSCA calls in dialogue with all relevant stakeholders, making responsible use of the options outlined below, to enlarge and modernize the notion of excellence (as done with the Gender dimension). Reward applicants and organisations that engage in open and responsible research through public engagement, science education, open science and ethical research; Provide (online) training for evaluators on implicit bias to reduce the risks of perpetuating narrow interpretations of research excellence in their evaluations; Offer training within the MSCA programme, such as via Innovative Training Networks, to prepare researchers and organizations for open and responsible, academic as well as non-academic careers. This includes a focus on transferable skills such as leadership and community engagement and attention to societal challenges; Reward and showcase MSCA grantees who excel in multiple dimensions of research, teaching, and service by showcasing and rewarding their work prominently on the MSCA website and social media; Support knowledge exchange and communities of practice around diverse and inclusive forms of excellence by involving a wide range of stakeholders (including civil society) in the ongoing discussion around modernizing and diversifying the concepts of excellence, and what counts as good and impactful academic practice. [ this is an excerpt, see pdf below for full policy brief ] For more from the Marie Curie Alumni Association, please see: https://zenodo.org/communities/mca

In vivo biocompatibility and immunogenicity of metal-phenolic gelation

In vivo forming hydrogels are of interest for diverse biomedical applications due to their ease-of-use and minimal invasiveness and therefore high translational potential. Supramolecular hydrogels that can be assembled using metal–phenolic coordination of naturally occurring polyphenols and group IV metal ions (e.g. TiIV or ZrIV) provide a versatile and robust platform for engineering such materials. However, the in situ formation and in vivo response to this new class of materials has not yet been reported. Here, we demonstrate that metal–phenolic supramolecular gelation occurs successfully in vivo and we investigate the host response to the material over 14 weeks. The TiIV–tannic acid materials form stable gels that are well-tolerated following subcutaneous injection. Histology reveals a mild foreign body reaction, and titanium biodistribution studies show low accumulation in distal tissues. Compared to poloxamer-based hydrogels (commonly used for in vivo gelation), TiIV–tannic acid materials show substantially improved in vitro drug loading and release profile for the corticosteroid dexamethasone (from 10 days). These results provide essential in vivo characterization for this new class of metal–phenolic hydrogels, and highlight their potential suitability for biomedical applications in areas such as drug delivery and regenerative medicine.<br

Controlling the growth of metal-organic frameworks using different gravitational forces

Control over Metal-organic framework (MOF) size and morphology is interesting for both fundamental and applied science. Gravitational force (g) is generally acknowledged as an interesting parameter for controlling crystal size; however, a dedicated study on the effect of g on MOF synthesis is missing. Here, we investigate the effect of varied g (< 1, 1, 20, 50, and 100) during the crystallization of different MOFs [ZIF-8, Tb2(BDC)3 and HKUST-1] in solution. The obtained MOFs were investigated using dynamic light scattering (DLS), X-ray scattering (SAXS and WAXS), and scanning electron and optical microscopy (SEM and OM, respectively). When compared with standard g (g = 1), high g (g = 20) gave rise to the formation of smaller MOF crystals, while low g (g < 1) led to larger crystals likely due to facet-oriented crystal fusion. This demonstrates that gravity and g-force can be used to rationally control the size of different MOFs by increasing or decreasing convection (mass transfer) and sedimentation.Joseph J. Richardson, Kang Liang, Fabio Lisi, Mattias Bjornmalm, Matthew Faria, Junling Guo, and Paolo Falcar

Bridging Bio-Nano Science and Cancer Nanomedicine

The interface of bio-nano science and cancer medicine is an area experiencing much progress but also beset with controversy. Core concepts of the field-e.g., the enhanced permeability and retention (EPR) effect, tumor targeting and accumulation, and even the purpose of "nano" in cancer medicine-are hotly debated. In parallel, considerable advances in neighboring fields are occurring rapidly, including the recent progress of "immuno-oncology" and the fundamental impact it is having on our understanding and the clinical treatment of the group of diseases collectively known as cancer. Herein, we (i) revisit how cancer is commonly treated in the clinic and how this relates to nanomedicine; (ii) examine the ongoing debate on the relevance of the EPR effect and tumor targeting; (iii) highlight ways to improve the next-generation of nanomedicines; and (iv) discuss the emerging concept of working with (and not against) biology. While discussing these controversies, challenges, emerging concepts, and opportunities, we explore new directions for the field of cancer nanomedicine

Gel-mediated electrospray assembly of silica supraparticles for sustained drug delivery

Supraparticles (SPs) composed of smaller colloidal particles provide a platform for the long-term, controlled release of therapeutics in biomedical applications. However, current synthesis methods used to achieve high drug loading and those involving biocompatible materials are often tedious and low throughput, thereby limiting the translation of SPs to diverse applications. Herein, we present a simple, effective, and automatable alginate-mediated electrospray technique for the assembly of robust spherical silica SPs (Si-SPs) for long-term (>4 months) drug delivery. The Si-SPs are composed of either porous or nonporous primary Si particles within a decomposable alginate matrix. The size and shape of the Si-SPs can be tailored by controlling the concentrations of alginate and silica primary particles used and key electrospraying parameters, such as flow rate, voltage, and collector distance. Furthermore, the performance (including drug loading kinetics, loading capacity, loading efficiency, and drug release) of the Si-SPs can be tuned by changing the porosity of the primary particles and through the retention or removal (via calcination) of the alginate matrix. The structure and morphology of the Si-SPs were characterized by electron microscopy, dynamic light scattering, N2 adsorption-desorption analysis, and X-ray photoelectron spectroscopy. The cytotoxicity and degradability of the Si-SPs were also examined. Drug loading kinetics and loading capacity for six different types of Si-SPs, using a model protein drug (fluorescently labeled lysozyme), demonstrate that Si-SPs prepared from primary silica particles with large pores can load significant amounts of lysozyme (∼10 μg per SP) and exhibit sustained, long-term release of more than 150 days. Our experiments show that Si-SPs can be produced through a gel-mediated electrospray technique that is robust and automatable (important for clinical translation and commercialization) and that they present a promising platform for long-term drug delivery

Minimum information reporting on bio-nano experimental literature

Studying the interactions between nanoengineered materials and biological systems plays a vital role in the development of biological applications of nanotechnology and the improvement of our fundamental understanding of the bio–nano interface. A significant barrier to progress in this multidisciplinary area is the variability of published literature with regards to characterizations performed and experimental details reported. Here, we suggest a ‘minimum information standard’ for experimental literature investigating bio–nano interactions. This standard consists of specific components to be reported, divided into three categories: material characterization, biological characterization and details of experimental protocols. Our intention is for these proposed standards to improve reproducibility, increase quantitative comparisons of bio–nano materials, and facilitate meta analyses and in silico modelling