Solid lipid nanoparticles (SLN) have been intensively exploited as nanocarriers for pulmonary drug delivery. However, no consensus on the underlying mechanisms between particle sizes and cell uptake behaviors was attained owing to their unclear in vivo fate after inhalation, which hindered the further development of a novel nanoparticle delivery system. Recently, aggregation-caused quenching (ACQ) probes had been developed to monitor the integrity of nanocarriers. In this study, an ACQ probe, P4, was employed to clarify the effect of particle size on SLN cellular uptake. SLN (120, 240, and 480 nm in size), incubated with epithelium cells (A549) and macrophages (RAW 264.7), mainly localized in the cytoplasm in an integrated pattern, showing a positive correlation relationship between particle size and cellular intake. In conclusion, this study established a firm basis to understand the effect of particle size on cellular uptake of nanoparticle systems and promoted the development of novel pulmonary drug delivery systems.

固体脂质纳米颗粒 (SLN) 已被广泛用作肺部药物递送的纳米载体。然而，由于颗粒大小和细胞摄取行为之间的潜在机制尚未达成共识，因为它们在吸入后的体内命运尚不清楚，这阻碍了新型纳米颗粒递送系统的进一步发展。最近，已经开发了聚集引起的猝灭 (ACQ) 探针来监测纳米载体的完整性。在这项研究中，使用 ACQ 探针 P4 来阐明粒径对 SLN 细胞摄取的影响。SLN（大小为 120、240 和 480 nm），与上皮细胞 (A549) 和巨噬细胞 (RAW 264.7) 一起孵育，主要以整合模式定位在细胞质中，显示出粒径与细胞摄入量之间的正相关关系。综上所述，