Engineered red blood cells (activating antigen carriers) drive potent T cell responses and tumor regression in mice.

Activation of T cell responses is essential for effective tumor clearance; however, inducing targeted, potent antigen presentation to stimulate T cell responses remains challenging. We generated Activating Antigen Carriers (AACs) by engineering red blood cells (RBCs) to encapsulate relevant tumor antigens and the adjuvant polyinosinic-polycytidylic acid (poly I:C), for use as a tumor-specific cancer vaccine. The processing method and conditions used to create the AACs promote phosphatidylserine exposure on RBCs and thus harness the natural process of aged RBC clearance to enable targeting of the AACs to endogenous professional antigen presenting cells (APCs) without the use of chemicals or viral vectors. AAC uptake, antigen processing, and presentation by APCs drive antigen-specific activation of T cells, both in mouse in vivo and human in vitro systems, promoting polyfunctionality of CD8+ T cells and, in a tumor model, driving high levels of antigen-specific CD8+ T cell infiltration and tumor killing. The efficacy of AAC therapy was further enhanced by combination with the chemotherapeutic agent Cisplatin. In summary, these findings support AACs as a potential vector-free immunotherapy strategy to enable potent antigen presentation and T cell stimulation by endogenous APCs with broad therapeutic potential.

Zinc oxide/silver nanoarrays as reusable SERS substrates with controllable 'hot-spots' for highly reproducible molecular sensing.

HYPOTHESIS: The reproducible surface enhanced Raman scattering (SERS)-based sensing of an analyte relies on high quality SERS substrates that offer uniformity over large areas. Uniform ZnO nanoarrays are expected to offer an appropriate platform for SERS sensing. Moreover, since ZnO has good photocatalytic properties, controllable decoration of silver nanoparticles on ZnO nanoarrays may offer an additional opportunity to clean up SERS substrates after each sensing event. EXPERIMENTS: This study employs a facile soft chemical synthesis strategy to fabricate Raman-active and recyclable ZnO/Ag nanorod arrays as reproducible SERS substrates. Arrays of ZnO nanorods were synthesized using hydrothermal method, which was followed by controllable decoration of ZnO with silver nanoparticles (AgNPs) using an electroless plating technique. FINDINGS: The uniform density of SERS-active 'hot-spots' on ZnO nanoarrays could be controlled on a large 1×1 cm(2) substrate. These ZnO/Ag nanoarrays showed high reproducibility (0.132 RSD) towards acquiring SERS spectra of rhodamine B (RB) at 30 random locations on a single substrate. The photocatalytic nature of ZnO/Ag semiconductor/metal hybrid endowed these substrates with reusability characteristics. By controlling metal loading on a semiconductor surface, photocatalytic activity and high SERS performance can be integrated within a single package to obtain high quality, reproducible, stable and recyclable SERS substrates.