In this project an extensive review of the scientific literature about nanoparticles and microneedles for the immunotherapy of cancer was made. From this extensive literature research two manuscripts were drafted and published in peer-reviewed open access scientific journals (see below). These review articles provide a wide scientific public novel insights, based on the most recent data from the scientific literature.
- Liposome-Based Drug Delivery Systems in Cancer Immunotherapy (Pharmaceutics 2020, 12(11):1054), were different liposomal systems specifically developed for immunomodulation in cancer are summarized and discussed (i.e. Vaccination, Tumor normalization, Rewiring of tumor signaling, and Combinational therapy).
- Cationic Nanoparticle-Based Cancer Vaccines (Pharmaceutics 2021, 13(5):596), where the relation between the cationic nature of nanoparticles and the efficacy of cancer immunotherapy are discussed as well as Multiple types of lipid- and polymer-based cationic nanoparticulate cancer vaccines with various antigen types (e.g. mRNA, DNA, peptides and proteins). Moreover, in this review the types of cationic nanoparticles used for T-cell induction, especially in the context of therapeutic cancer vaccination are discussed.
Furthermore, a new method and system was developed to fabricate novel dissolvable microneedle structures on a verry controlled manner via nanolitre-size droplets. Based on this work a manuscript was prepared, which was published in a peer reviewed journal (Int J Pharm 2021, 600:120473). The published system and methodology are currently being further exploited for their potential use for intradermal cancer immunotherapy.
In this project a novel hollow microneedle system was developed for LOCAL delivery of nanoparticles as well as lipid nanoparticles containing an immunomodulating drug (STING agonist). The lipid nanoparticles have shown to be very potent in cell assays and the hollow microneedle system enabled us to inject volumes below 1 µL accurately into a solid tumour. Follow up experiments are planned to investigate the efficacy of intratumorally injected lipid nanoparticles for tumor regression in animal studies.
Finally, in this project a wide range of lipid nanoparticles were synthesized, which were formulated with a near-infrared fluorescent dye and a peptide-based cancer vaccine. These nanoparticles were evaluated in cell cultures and animals for the induction of cancer-specific immune responses and tumour control. From these studies a selection of potent cancer vaccine candidates were obtained that induced high cancer-specific immune responses and showed effective tumour control (manuscript in preparation).
