Personalized cancer vaccines (PCVs) targeting patient-specific neoantigens are a promising cancer treatment modality; however, neoantigen physicochemical variability can present challenges to manufacturing PCVs in an optimal format for inducing anticancer T cells. Here, we developed a vaccine platform ("SNP-7/8a") based on charge-modified peptide-TLR-7/8a conjugates that are chemically programmed to self-assemble into nanoparticles of uniform size (~20 nm) irrespective of the peptide antigen composition. This approach provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticles that increased uptake by and activation of antigen-presenting cells that promote T cell immunity. Vaccination of mice with SNP-7/8a using predicted neoantigens (n=179) from three tumor models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity and led to enhanced tumor clearance. SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in non-human primates. Altogether, SNP-7/8a is a generalizable approach for co-delivering peptide antigens and adjuvants in nanoparticles for inducing anticancer T cell immunity.
The stability or wettability of thin polymer films on solids is of vital interest in traditional technologies as well as in new emerging nanotechnologies. We report here that nanoscale structures of polymer chains adsorbed onto a solid surface play a crucial role in the thermal stability of the film. In this study, polystyrene (PS) spin-cast films (20 nm in thickness) with eight different molecular weights prepared on silicon (Si) substrates were used as a model. When low molecular weight (Mw≤ 50 kDa) PS films were subjected to thermal annealing at temperatures far above the bulk glass transition temperature, dewetting occurred promptly, while high molecular weight (Mw≥ 123 kDa) PS films were stable for at least 6 weeks at 150 °C. We reveal a strong correlation between the film stability and the two different interfacial structures of the adsorbed polymer chains: their opposing wettability against chemically identical free polymer chains results in a wetting-dewetting transition at the adsorbed polymer-free polymer interface. This is a unique aspect of the stability of polymer thin films and may be generalizable to other polymer systems regardless of the magnitude of solid-polymer attractive interactions.
We report the structural relaxation process of irreversibly adsorbed polymer chains via thermal annealing that lie flat on a solid (“flattened chains”). Amorphous polystyrene and quartz, which together constitute a weakly attractive system, was used as a model where the local chain conformations of the flattened chains were investigated by sum frequency generation spectroscopy (SFG). Two different film preparation processes (i.e., spin coating and dip coating methods) were utilized to create different initial chain conformations. The spin-coated and dip-coated PS thin films were annealed at a temperature far above the bulk glass transition temperature to reach the “quasiequilibrium” state and subsequently rinsed with chloroform to uncover the buried flattened chains. The SFG results revealed that the backbone chains (constituted of CH and CH2 groups) of the flattened PS chains preferentially orient to the weakly interactive substrate surface via thermal annealing regardless of the initial chain conformations, while the orientation of the phenyl rings becomes randomized. We postulate that increasing the number of surface-segmental contacts (i.e., enthalpic gain) is the driving force for the flattening process of the polymer chains, even onto a weakly interactive solid to overcome the conformational entropy loss in the total free energy.
Here we report a link between the interfacial structure and adhesive property of homopolymer chains physically adsorbed (i.e., via physisorption) onto solids. Polyethylene oxide (PEO) was used as a model and two different chain conformations of the adsorbed polymer were created on silicon substrates via the well-established Guiselin's approach: "flattened chains" which lie flat on the solid and are densely packed, and "loosely adsorbed polymer chains" which form bridges jointing up nearby empty sites on the solid surface and cover the flattened chains. We investigated the adhesion properties of the two different adsorbed chains using a custom-built adhesion testing device. Bilayers of a thick PEO overlayer on top of the flattened chains or loosely adsorbed chains were subjected to the adhesion test. The results revealed that the flattened chains do not show any adhesion even with the chemically identical free polymer on top, while the loosely adsorbed chains exhibit adhesion. Neutron reflectivity experiments corroborated that the difference in the interfacial adhesion is not attributed to the interfacial brodening at the free polymer-adsorbed polymer interface. Instead, coarse-grained molecular dynamics simulation results suggest that the tail parts of the loosely adsorbed chains act as "connector molecules", bridging the free chains and substrate surface and improving the interfacial adhesion. These findings not only shed light on the structure-property relationship at the interface, but also provide a novel approach for developing sticking/anti-sticking technologies through precise control of the interfacial polymer nanostructures.
Congenital granular cell epulis (CGCE) is an uncommon lesion of unclear pathogenesis. It occurs predominantly in female newborns with a predilection site of the maxillary alveolar ridge. The mass enlarges prenatally but the growth arrests after birth. Histologically, CGCE is characterized by a proliferation of polygonal cells with eosinophilic, granular cytoplasm and eccentric, bland-appearing nuclei. It closely resembles adult granular cell tumor (GCT) microscopically and S-100 immunostain is often helpful in distinguishing the two (S-100-positive in GCT and S-100-negative in CGCE). Clinically, the lesion should also be distinguished from entities such as infantile myofibroma, rhabdomyoma, melanotic neuroectodermal tumor of infancy, peripheral odontogenic fibroma, and neurofibroma. CGCE demonstrates an excellent prognosis and has not been associated with any syndromes/genetic defects or malignant transformation. Clinicians and pathologists should be familiar with this rare entity and its differential diagnosis for accurate diagnosis and management.
The solid–polymer melt interface is of great scientific interest due to its vital importance in governing a wide array of physical and mechanical properties of polymer thin films. Recent studies have elucidated the coexistence of two different chain conformations of polymer chains adsorbed on a solid (i.e., loosely adsorbed chains and flattened chains). In this work, film stabilities of the polystyrene (PS) “interfacial sublayer” (composed of outer loosely adsorbed chains and inner flattened chains) and flattened layer (composed of the lone flattened chains) prepared on silicon (Si) substrates are investigated. The atomic force microscopy studies reveal that the as‐rinsed PS flattened layer is subjected to spinodal‐like dewetting during a post‐thermal annealing process even at temperatures below the bulk glass transition temperature. Furthermore, it is found that the surface morphology of the flattened layer can be reversibly changed from a homogeneous pattern under good solvent conditions to spinodal‐like droplets under poor solvent conditions. By contrast, it is found that the PS interfacial sublayer remains stable under both good and poor solvent conditions. These findings illuminate the role which density variations within the adsorbed layers play in the mechanism behind the wetting‐dewetting transition.
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