Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) could treat Imiquimod (IMQ)-induced psoriasis-like mice. The objective of this study is to further elucidate biofate of PLGA NPs after intradermal delivery including DCs uptake, and their further trafficking in psoriasis-like mice model by using fluorescence probes. Two-sized DiO/DiI-loaded PLGA NPs of 50 ± 4.9 nm (S-NPs) and 226 ± 7.8 nm (L-NPs) were fabricated, respectively. In vitro cellular uptake results showed that NPs could be internalized into DCs with intact form, and DCs preferred to uptake larger NPs. Consistently, in vivo study showed that L-NPs were more captured by DCs and NPs were firstly transported to skin-draining lymph nodes (SDLN), then to spleens after 8 h injection, whereas more S-NPs were transported into SDLN and spleens. Moreover, FRET imaging showed more structurally intact L-NPs distributed in skins and lymph nodes. In conclusion, particle size can affect the uptake and trafficking of NPs by DCs in skin and lymphoid system, which needs to be considered in NPs tailing to treat inflammatory skin disease like psoriasis.

牛皮癣是一种自身免疫性炎性疾病，其中树突状细胞（DC）在其发病机理中起重要作用。在我们以前的工作中，我们已经证明，负载姜黄素聚（乳酸-局部递送共-glycolic酸）（PLGA）纳米颗粒（NP）可以治疗咪喹莫特（IMQ）银屑病样小鼠诱导。这项研究的目的是进一步阐明PLGA NP在皮内递送后的生物命运，包括DC的摄取，以及它们通过使用荧光探针在牛皮癣样小鼠模型中的进一步运输。分别制作了两种尺寸的DiO / DiI负载PLGA NP，分别为50±4.9 nm（S-NP）和226±7.8 nm（L-NP）。体外细胞摄取结果显示，NPs可以以完整形式内在化为DC，DC则更倾向于摄取较大的NP。始终如一体内研究表明，L-NPs被DC捕获的量更多，并且NPs首先被输送至皮肤引流淋巴结（SDLN），然后在注射8 h后被输送至脾脏，而更多的S-NPs被输送至SDLN和脾脏。此外，FRET成像显示更多结构完整的L-NP分布在皮肤和淋巴结中。总之，粒径可影响皮肤和淋巴系统中DC摄取和运输NP的能力，在NP拖尾以治疗诸如牛皮癣之类的炎性皮肤疾病时需要考虑粒径。