Publications

Interactions between living cells and nanoparticles are extensively studied to enhance the delivery of therapeutics. Nanoparticles size, shape, stiffness, and surface charge are regarded as the main features able to control the fate of cell-nanoparticle interactions. However, the clinical translation of nanotherapies has so far been limited, and there is a need to better understand the biology of cell-nanoparticle interactions. This study investigates the role of cellular mechanosensitive components in cell-nanoparticle interactions. It is demonstrated that the genetic and pharmacologic inhibition of yes-associated protein (YAP), a key component of cancer cell mechanosensing apparatus and Hippo pathway effector, improves nanoparticle internalization in triple-negative breast cancer cells regardless of nanoparticle properties or substrate characteristics. This process occurs through YAP-dependent regulation of endocytic pathways, cell mechanics, and membrane organization. Hence, the study proposes targeting YAP may sensitize triple-negative breast cancer cells to chemotherapy and increase the selectivity of nanotherapy.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

JTD Keywords: cancer treatment, cells, differentiation, hippo pathway, mechanics, mechanobiology, mechanotransduction, nanoparticles, progression, protein, resistance, yap-signaling, yap/taz, Adaptor proteins, signal transducing, Bio-nano interaction, Bio-nano interactions, Breast cancer cells, Cancer cells, Cancer treatment, Cells, Cellular therapeutics, Cellular uptake, Chemotherapy, Cytology, Diseases, Extracellular-matrix, Human, Humans, Mechano-biology, Mechanobiology, Metabolism, Nanoparticle, Nanoparticle interaction, Nanoparticles, Physiology, Protein serine threonine kinase, Protein serine-threonine kinases, Protein signaling, Signal transducing adaptor protein, Signal transduction, Therapeutic effects, Triple negative breast cancer, Triple negative breast neoplasms, Triple-negative breast cancers, Yap-signaling, Yap-signaling proteins, Yes-associated protein-signaling

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A–B Niemann–Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications.

JTD Keywords: active enzymes, encapsulation, enhanced delivery, enzyme therapeutics, formulation parameters, icam-1 targeting, icam-1-targeted nanocarriers, in vivo biodistribution, in-vitro, lysosomal delivery, model, oral delivery, plga nanoparticles, poly(lactic-co-glycolic acid) nanoparticles, protein therapeutics, surface loading, Acid sphingomyelinase, Enzyme therapeutics, Surface loading

A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields. © 2021 American Chemical Society.

JTD Keywords: biodegradable dextran hydrogels, biotherapeutics, bone morphogenetic protein-2, carrageenan-based hydrogels, chitosan-based hydrogels, controlled delivery, controlled-release, cross-linked hydrogels, growth-factor delivery, hydrogels, in-vitro characterization, polysaccharides, self-healing hydrogel, stimuli-responsiveness, tissue engineering, Antibodies, Bioactivity, Biodegradability, Biomedical fields, Biomolecules, Biotherapeutics, Chemical modification, Circular economy, Controlled delivery, Controlled drug delivery, Delivery systems, Drug delivery system, Functional polymers, Hyaluronic-acid hydrogels, Hydrogels, Industrial processs, Polysaccharides, Recent progress, Renewable sources, Stimuli-responsiveness, Targeted drug delivery, Tissue engineering, Waste management

The rational design of nanomedicines is a challenging task given the complex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these materials with the biological environment. Herein, an unexpected charge-like attraction mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous “ordinary–extraordinary” phenomenon previously described by physicists. For the first time, a bottom-up methodology for the stabilization of these nanosized soft-assembled star-shaped polyglutamates is also described, enabling the translation of theoretical research into nanomaterials with applicability within the drug-delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug-delivery systems highlight the potential of this approach for tumor-localized as well as lymphotropic delivery.

JTD Keywords: Charge-like, Drug delivery, Polymer therapeutics, Polypeptides, Self-assembly

Sleep science and respiratory engineering as medical subspecialties and research areas grew up side-by-side with biomedical engineering. The formation of EMBS in the 1950's and the discovery of REM sleep in the 1950's led to parallel development and interaction of sleep and biomedical engineering in diagnostics and therapeutics.

JTD Keywords: Practical/ biomedical equipment, Biomedical measurement, Patient diagnosis, Patient monitoring, Patient treatment, Pneumodynamics, Sleep/ sleep engineering, Respiratory engineering, Automatic sleep analysis, Automatic sleep interpretation systems, Breathing, Biomedical, Engineering, Diagnostics, Therapeutics, REM sleep, Portable, Measurement, Ambulatory measurement, Monitoring