Immunogenic lipid-coated mesoporous silica nanoparticles (ILM) present pathogen-associated molecular patterns (PAMPs) on the nanoparticle surface to engage pathogen-associated receptors on immune cells. The mesoporous core is capable of loading additional immunogens, antigens or drugs. In this study, the impact of lipid composition, surface potential and intercalation of lipophilic monophosphoryl lipid A (MPL-A) in the lipid coat on nanoparticle properties and cellular interactions is presented. Loading and retention of the model antigen ovalbumin into the mesoporous silica core were found to be similar for all nanoparticle formulations, with presentation of ova peptide (SIINFEKL) by major histocompatibility complex (MHC) evaluated to facilitate the selection of an anionic nanoparticle composition. ILM were able to induce lysosomal tubulation and streaming of lysosomes towards the cell surface in dendritic cells, leading to an enhanced surface presentation of MHC. Myeloid cells robustly internalized all ILM formulations; however, non-myeloid cells selectively internalized cationic ILM in vitro in the presence of 20% serum. Interestingly, ILM administration to the peritoneal cavity of mice with disseminated ovarian cancer resulted in selective accumulation of ILM in tumor-associated tissues (>80%), regardless of nanoparticle surface charge or the presence of MPL-A. Immunofluorescence analysis of the omental tumor showed that ILMs, regardless of surface charge, were localized within clusters of CD11b+myeloid cells 24 h post administration. Selective uptake of ILMs by myeloid cells in vivo indicates that these cells outcompete other cell populations in the ovarian tumor microenvironment, making them a strong target for therapeutic interventions.
免疫原性脂质包被介孔二氧化硅纳米颗粒（ILM）在纳米颗粒表面呈现病原体相关分子模式（PAMPs），以结合免疫细胞上的病原体相关受体。其介孔核心能够负载额外的免疫原、抗原或药物。本研究探讨了脂质组成、表面电位及脂质包被中亲脂性单磷酰脂质A（MPL-A）的嵌入对纳米颗粒性质及细胞相互作用的影响。研究发现，所有纳米颗粒制剂对模型抗原卵清蛋白的负载与保留能力相似，通过评估主要组织相容性复合体（MHC）呈递卵清蛋白肽（SIINFEKL）的能力，筛选出阴离子纳米颗粒配方。ILM能够诱导树突状细胞中溶酶体管状化并驱动溶酶体向细胞表面流动，从而增强MHC的表面呈递。髓系细胞对所有ILM制剂均表现出强内吞作用；然而在20%血清存在条件下，非髓系细胞在体外选择性内吞阳离子ILM。值得注意的是，在播散性卵巢癌小鼠腹腔内注射ILM后，无论纳米颗粒表面电荷或MPL-A存在与否，ILM均选择性积聚于肿瘤相关组织（>80%）。给药24小时后网膜肿瘤的免疫荧光分析显示，无论表面电荷如何，ILM均定位于CD11b+髓系细胞簇内。体内髓系细胞对ILM的选择性摄取表明，这些细胞在卵巢肿瘤微环境中胜过其他细胞群体，使其成为治疗干预的重要靶点。
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