Antigen-specific T cell activation through targeted delivery of in-situ generated antigen and calcium ionophore to enhance antitumor immunotherapy.

Recent advances in adoptive T-cell therapy have delivered impressive therapeutic outcomes by instigating enduring anti-tumor responses. Nonetheless, achieving specific T-cell activation remains a challenge due to several factors. Some cancer cells evade T-cell recognition due to the scarcity of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) presentation. Notably underestimated is the impact of waning T-cell receptor (TCR) expression and the constrained formation of immune synapses (IS) between dendritic cells (DCs) and T cells, impairing T-cell activation. Addressing these complexities, we introduce a pioneering approach featuring the deployment of a gel implant. This implant establishes an on-site antigen reservoir, efficiently targets DCs in lymph nodes, and facilitates calcium ion (Ca2+) delivery. Engineered with controlled swelling, poroelasticity, and resilience, the gel is suitable for surgical implantation. Its ample encapsulation capacity accommodates both photosensitizers and nanoparticles. Upon in situ photothermal irradiation, the gel generates tumor-specific antigens. Furthermore, cationic albumin nanoparticles (cNPs) co-loaded with monophosphoryl lipid A (MPLA) and ionomycin are released, guiding antigens to tumor-draining lymph nodes for DCs maturation. This meticulous process fosters the formation of IS thereby amplifying antigen-specific T-cell activation.

Effect of Albumin Corona Conformation on In Vitro and In Vivo Profiles of Intravenously Administered Nanoparticles.

Under physiological conditions, nanoparticles (NPs) inevitably interact with proteins, resulting in extensive protein adsorption and the formation of a protein corona. Recent studies have shown that the different surface properties of NPs lead to varying degrees of conformational changes of adsorbed proteins. However, the impact of corona protein conformation on the in vitro and in vivo profiles of NPs remain largely unexplored. Herein, d-α-tocopherol polyethylene glycol 1000 succinate-based NPs with natural human serum albumin (HSAN) corona or thermally denatured HSA (HSAD) corona were synthesized following a previously established method. We then conducted a systematic study of the protein conformation as well as adsorption behaviors. Additionally, the impact of protein corona conformation on the NPs profiles in vitro and in vivo were elucidated to gain insight into its biological behaviors as a targeted delivery system for renal tubule diseases. Overall, NPs modified by HSAN corona showed improved serum stability, greater cell uptake efficiency, better renal tubular targetability, and therapeutic efficacy on acute kidney injury in rats than NPs modified by HSAD corona. Hence, the conformation of protein adsorbed on the surface of NPs may impact the in vitro and in vivo profiles of NPs.