Cationic polymers are widely used materials in diverse biotechnologies. Subtle variations in these polymers' properties can change them from exceptional delivery agents to toxic inflammatory hazards. Conventional screening strategies optimize for function in a specific application rather than observing how underlying polymer-cell interactions emerge from polymers' properties. An alternative approach is to map basic underlying responses, such as immunogenicity or toxicity, as a function of basic physicochemical parameters to inform the design of materials for a breadth of applications. To demonstrate the potential of this approach, we synthesized 107 polymers varied in charge, hydrophobicity, and molecular weight. We then screened this library for cytotoxic behavior and immunogenic responses to map how these physicochemical properties inform polymer-cell interactions. We identify three compositional regions of interest and use confocal microscopy to uncover the mechanisms behind the observed responses. Finally, immunogenic activity is confirmed in vivo. Highly cationic polymers disrupted the cellular plasma membrane to induce a toxic phenotype, while high molecular weight, hydrophobic polymers were uptaken by active transport to induce NLRP3 inflammasome activation, an immunogenic phenotype. Tertiary amine- and triethylene glycol-containing polymers did not invoke immunogenic or toxic responses. The framework described herein allows for the systematic characterization of new cationic materials with different physicochemical properties for applications ranging from drug and gene delivery to antimicrobial coatings and tissue scaffolds.

Activating innate immunity in a controlled manner is necessary for the development of next-generation therapeutics. Adjuvants, or molecules that modulate the immune response, are critical components of vaccines and immunotherapies. While small molecules and biologics dominate the adjuvant market, emerging evidence supports the use of immunostimulatory polymers in therapeutics. Such polymers can stabilize and deliver cargo while stimulating the immune system by functioning as pattern recognition receptor (PRR) agonists. At the same time, in designing polymers that engage the immune system, it is important to consider any unintended initiation of an immune response that results in adverse immune-related events. Here, we highlight biologically derived and synthetic polymer scaffolds, as well as polymer-adjuvant systems and stimuli-responsive polymers loaded with adjuvants, that can invoke an immune response. We present synthetic considerations for the design of such immunostimulatory polymers, outline methods to target their delivery, and discuss their application in therapeutics. Finally, we conclude with our opinions on the design of next-generation immunostimulatory polymers, new applications of immunostimulatory polymers, and the development of improved preclinical immunocompatibility tests for new polymers.

Diamond has superlative material properties for a broad range of quantum and electronic technologies. However, heteroepitaxial growth of single crystal diamond remains limited, impeding integration and evolution of diamond-based technologies. Here, we directly bond single-crystal diamond membranes to a wide variety of materials including silicon, fused silica, sapphire, thermal oxide, and lithium niobate. Our bonding process combines customized membrane synthesis, transfer, and dry surface functionalization, allowing for minimal contamination while providing pathways for near unity yield and scalability. We generate bonded crystalline membranes with thickness as low as 10 nm, sub-nm interfacial regions, and nanometer-scale thickness variability over 200 by 200 μm² areas. We measure spin coherence times T₂ for nitrogen vacancy centers in 150 nm-thick bonded membranes of up to 623 ± 21 μs, suitable for advanced quantum applications. We demonstrate multiple methods for integrating high quality factor nanophotonic cavities with the diamond heterostructures, highlighting the platform versatility in quantum photonic applications. Furthermore, we show that our ultra-thin diamond membranes are compatible with total internal reflection fluorescence (TIRF) microscopy, which enables interfacing coherent diamond quantum sensors with living cells while rejecting unwanted background luminescence. The processes demonstrated herein provide a full toolkit to synthesize heterogeneous diamond-based hybrid systems for quantum and electronic technologies.