Kakizawa Yoshinori, Lee Jung Seok, Bell Brendan, Fahmy Tarek M
Department of Biomedical Engineering, School of Engineering and Applied Sciences, Yale University, New Haven, CT 06511, USA; New Frontiers Research Laboratories, Toray Industries, Inc., Kanagawa 248-8555, Japan.
Department of Biomedical Engineering, School of Engineering and Applied Sciences, Yale University, New Haven, CT 06511, USA.
Acta Biomater. 2017 Jul 15;57:136-145. doi: 10.1016/j.actbio.2017.01.025. Epub 2017 Jan 6.
The biophysical parameters governing nanoparticle (NP)-cell interactions significantly affect biological responses, particularly in the application of NP-based immunotherapeutics. Modulation of the surface biophysical character of NPs can be achieved via introduction of amino acids, which offer the ability to fine tune a range of biophysical parameters of interest. We employed this approach using monodisperse silica NPs coated with numerous poly(amino acid)s (PAAs). The NPs were incubated with dendritic cells (DCs) in conjunction with TLR ligands and production of IL-1β from DCs and IFNγ from T cells primed by these DCs were measured. These key cytokines can prognosticate the efficacy of the NP platform as a potential vaccine or active cellular immunotherapy carrier. IL-1β production showed a correlation with both NP size and degree of hydrophobicity. High IFNγ secretion from T cells was shown to be correlated with both the hydrophobicity and charge of the NPs used to activate the DCs. Other cytokines were also screened in order to compare the immune responses. The results of this study highlight the importance of nanoparticle biophysical parameters and the selection of TLR ligands to the rational design of nanoparticle-based vaccines and immunotherapies.
The manuscript describes a systematic investigation into the effects of biophysical parameters of nanoparticles (NPs) on immune cells. Modulation of the biophysical character of the NP surface can be achieved by introduction of amino acids on monodisperse silica NPs, introducing a range of tunable biophysical parameters of interest, i.e. distinct sizes, different surface charges and varying degrees of surface hydrophobicity. We examine internalization of the NP in dendritic cells (DCs) and measure a myriad of cytokines, including IL-1β and IFNγ, which prognosticate the efficacy of the NPs as a potential vaccine (IL-1β metric) or active cellular immunotherapy carrier (IFNγ metric). Two different TLR ligands (a viral TLR3 ligand and a bacterial TLR4 ligand) were used along with the PAA NPs to compare their costimulatory immunogenicity. We strongly believe that this study will provide crucial information to many readers of Acta Biomaterialia and further drive the use of nanoparticle platforms in modulating immune responses.
控制纳米颗粒（NP）与细胞相互作用的生物物理参数会显著影响生物学反应，尤其是在基于NP的免疫治疗应用中。通过引入氨基酸可以实现对NP表面生物物理特性的调节，这能够对一系列感兴趣的生物物理参数进行微调。我们采用这种方法，使用涂覆有多种聚氨基酸（PAA）的单分散二氧化硅NP。将这些NP与树突状细胞（DC）一起孵育，并结合Toll样受体（TLR）配体，测量DC产生的白细胞介素-1β（IL-1β）以及由这些DC启动的T细胞产生的干扰素γ（IFNγ）。这些关键细胞因子可以预测NP平台作为潜在疫苗或活性细胞免疫治疗载体的功效。IL-1β的产生与NP大小和疏水性程度均相关。T细胞中高IFNγ分泌显示与用于激活DC的NP的疏水性和电荷均相关。还筛选了其他细胞因子以比较免疫反应。本研究结果突出了纳米颗粒生物物理参数以及TLR配体的选择对于基于纳米颗粒的疫苗和免疫治疗合理设计的重要性。
本文描述了对纳米颗粒（NP）生物物理参数对免疫细胞影响的系统研究。通过在单分散二氧化硅NP上引入氨基酸，可以实现对NP表面生物物理特性的调节，从而引入一系列感兴趣的可调生物物理参数，即不同的大小、不同的表面电荷和不同程度的表面疏水性。我们研究了NP在树突状细胞（DC）中的内化情况，并测量了多种细胞因子，包括IL-1β和IFNγ，它们可以预测NP作为潜在疫苗（IL-1β指标）或活性细胞免疫治疗载体（IFNγ指标）的功效。使用两种不同的TLR配体（一种病毒TLR3配体和一种细菌TLR4配体）与PAA NP一起比较它们的共刺激免疫原性。我们坚信这项研究将为《生物材料学报》的许多读者提供关键信息，并进一步推动纳米颗粒平台在调节免疫反应中的应用。
