Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.

Aging has profound effects on the body, most notably an increase in the prevalence of several diseases. An important aging hallmark is the presence of senescent cells that no longer multiply nor die off properly. Another characteristic is an altered immune system that fails to properly self-surveil.

Super Resolved Single-Cell Spatial Metabolomics from Multimodal Mass Spectrometry Imaging guided by Imaging Mass Cytometry.

Mass spectrometry imaging (MSI) is a powerful technique for spatially resolved analysis of metabolites and other biomolecules within biological titissues. However, the inherent low spatial resolution of MSI often limits its ability to provide detailed cellular-level information. To address this limitation, we propose a guided super-resolution (GSR) approach that leverages high-resolution Imaging Mass Cytometry (IMC) images to enhance the spatial resolution of low-resolution MSI data.

Spatially resolved subcellular protein-protein interactomics in drug-perturbed lung-cancer cultures and tissues.

Protein-protein interactions (PPIs) regulate signalling pathways and cell phenotypes, and the visualization of spatially resolved dynamics of PPIs would thus shed light on the activation and crosstalk of signalling networks. Here we report a method that leverages a sequential proximity ligation assay for the multiplexed profiling of PPIs with up to 47 proteins involved in multisignalling crosstalk pathways. We applied the method, followed by conventional immunofluorescence, to cell cultures and tissues of non-small-cell lung cancers with a mutated epidermal growth-factor receptor to determine the co-localization of PPIs in subcellular volumes and to reconstruct changes in the subcellular distributions of PPIs in response to perturbations by the tyrosine kinase inhibitor osimertinib.

Stimuli-responsive self-assembled polymer nanoparticles for the oral delivery of antibodies.

Currently, commercially available antibody therapies must be delivered via parenteral administration. Oral delivery of antibodies could increase patient compliance and improve quality of life, however there is currently no viable system for delivering antibodies orally. In this work, a self-assembled, pH-responsive nanoparticle delivery system was developed to load and deliver antibodies via the oral route.

Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic.

mRNA vaccines have received major attention in the fight against COVID-19. Formulations from companies such as Moderna and BioNTech/Pfizer have allowed us to slowly ease the social distancing measures, mask requirements, and lockdowns that have been prevalent since early 2020. This past year's focused work on mRNA vaccines has catapulted this technology to the forefront of public awareness and additional research pursuits, thus leading to new potential for bionanotechnology principles to help drive further innovation using mRNA.

Polymer Composition Primarily Determines the Protein Recognition Characteristics of Molecularly Imprinted Hydrogels.

Synthetic hydrogels with the ability to recognize and bind target proteins are useful for a number of applications, including biosensing and therapeutic agent delivery. One popular method for fabricating recognitive hydrogels is molecular imprinting. A long-standing hypothesis of the field is that these molecularly imprinted polymers (MIPs) retain the chemical and geometric profile of their protein template, resulting in subsequent ability to recognize the template in solution.

Peptide conjugation enhances the cellular co-localization, but not endosomal escape, of modular poly(acrylamide-co-methacrylic acid) nanogels.

Nanoparticles must recognize, adhere to, and/or traverse multiple barriers in sequence to achieve cytosolic drug delivery. New nanoparticles often exhibit a unique ability to cross a single barrier (i.e.

Synthetic networks with tunable responsiveness, biodegradation, and molecular recognition for precision medicine applications.

Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient's disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells.