Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical success.During ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor response.While effective,this process is resource-intensive and logistically impossible for many patients.Particulate artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo ACT.While particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after injection.Barriers to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of interest.Biomaterial properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell stimulation.Previous literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in vitro.With the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive transfer.Using this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

Flow behavior and deposition study of pollen-shape carrier particles in an idealized inhalation path model

Pollen-shape （spiked sphere） hydroxyapatite （HA） particles for drug carrier application are studied. The particle shape and size effect on flow characteristics and deposition are assessed. The pollen-shape HA particles are synthesized to have comparable size as typical carrier particles with mean diameter of 30-50 μm and effective density less than 0.3 g/cm^3. The flow behaviors of HA and commonly used lactose （LA） carrier particles are characterized by the Carr＇s compressibility index （CI）. The HA particles have lower CI than the LA particles for the same size range. The flow fields of HA and LA carrier particles are measured in an idealized inhalation path model using particle image velocimetry （PLY） technique. The particle streamlines indicate that a large portion of particles may deposit at the bending section due to inertial impaction and gravitational deposition. The flow field result shows that HA particles give smaller separation regions than the LA particles for the same size range. The pollen-shape HA particles are found to be able to follow the gas flow in the model and minimize undesired deposition. Deposition result confirms the bending section to have the most deposition. Deposition is found to be a function of particle properties. An empirical correlation is derived for the deposition efficiency of the pollen-shape particles as a function of particles Stokes number.