International Journal of Nanomedicine (Aug 2020)
Silica Nanocapsules with Different Sizes and Physicochemical Properties as Suitable Nanocarriers for Uptake in T-Cells
Abstract
Raweewan Thiramanas1,2 ,* Shuai Jiang2 ,* Johanna Simon,1,2 Katharina Landfester,2 Volker Mailänder1,2 1Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz 55131, Germany; 2Physical Chemistry of Polymers, Max Planck Institute for Polymer Research, Mainz, 55128, Germany*These authors contributed equally to this workCorrespondence: Katharina Landfester; Volker Mailänder Email [email protected]; [email protected]: Adoptive T-cell immunotherapy emerged as a powerful and promising cancer therapy, as the problem regarding the immuno-reaction between different donors and recipients can be avoided. However, this approach is challenging. After long cultivation and expansion under laboratory media conditions, T-cells are losing their viability and function due to immune checkpoint proteins, leading to decreased efficiency in killing cancer cells. Therefore, a new strategy to improve T-cell survival and function is needed. With the advantages of nanotechnology and the biocompatibility of silica-based material, silica nanocapsules (SiNCs) provide an ideal delivery system to transport therapeutic biomolecules to T-cells. Up to now, there is a lack of cellular uptake studies of nanocarriers towards T-cells.Methods: We systematically studied the influence of various physicochemical properties such as sizes, core hydrophobicities, surface charges, and surface functionalities of SiNC for their impact on cellular uptake and toxicity in CD8+ T-cells by flow cytometry and confocal laser scanning microscopy. Cytokine secretion assay was performed using the enzyme-linked immunosorbent assay. To identify suitable uptake conditions for SiNCs into CD8+ T-cells, the impact of human serum in cell culture medium was also investigated.Results: The major impact on cellular uptake and toxicity was found to be size- and dose-dependent. Smaller sizes of SiNCs than 100 nm caused significant toxicity to the cells. It was found that the formed protein corona reduced the toxicity of the SiNCs. However, it also inhibited their uptake.Conclusion: Overall, we present a set of different criteria for a suitable design of nanocarriers and cell culture conditions, which need to be carefully considered for T-cell immunotherapy in vitro to facilitate uptake while avoiding toxicity.Keywords: silica nanocapsule, T-cells, nanocarriers, cellular uptake, toxicity, protein corona
