Evaluation of functionalized nanoparticles for cellular uptake and their induction of antigenspecific immune responses

Abstract

Nanotechnology has emerged as a promising avenue for vaccine development, offering precise control of antigen delivery, and then induction and modulation of immune responses. The work that is subject to this thesis focused on the evaluation of functionalized nanoparticles (NP) designed for optimal uptake by antigen presenting cells (APCs) and subsequent induction of antigen-specific immune responses. The NPs were engineered with surface modifications to enhance their interactions with target cells. In this study, we conducted a systematic assessment of the efficacy of NPs, beginning with an exploration of their physicochemical properties and stability. Subsequently, their ability to enter immune cells was investigated, with a focus on their cellular uptake and intracellular trafficking. The studies dealt with in this thesis aimed to elucidate the impact of surface functionalizations on the ability of NPs to engage APCs, thereby influencing the efficiency of antigen presentation. For this purpose, different NPs were synthesized and functionalized by various collaborators with different biological components, such as i) antibodies to address specific immune cells, ii) antigens to be processed by APCs for presentation to T cells, and iii) adjuvants recognized through pattern recognition receptors (PRRs) that are required to stimulate APCs to induce T effector cells. In this case, NPs need to facilitate the co-delivery of antibodies, adjuvants, and antigens since all three components are required for a successful vaccination. Furthermore, the immunogenicity of the NPs was evaluated by a series of in vitro and in vivo experiments regarding their biodistribution, their ability to target APC and their capacity to induce antigen-specific T cell immune responses. These results highlight the potential of functionalized NPs to optimize vaccine design, with implications for the development of effective and targeted immunization approaches. In conclusion, this thesis provides valuable insights into the design and evaluation of functionalized NPs, shedding light on their cellular uptake mechanisms and their ability to elicit antigen-specific immune responses. These findings hold promise for improvement of vaccine development, offering innovative solutions for combating infectious diseases, and promoting a more targeted and robust immune response as for example in the context of tumor therapy. Keywords: Nanomedicine, nanoparticles, uptake, properties, cancer, adjuvant, antigen.