Lin Zibei, Xi Long, Chen Shaokui, Tao Jinsong, Wang Yan, Chen Xin, Li Ping, Wang Zhenping, Zheng Ying
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
Beijing Hospital of Traditional Chinese Medicine, Affiliated with Capital Medical University, Beijing 100050, China.
Acta Pharm Sin B. 2021 Apr;11(4):1047-1055. doi: 10.1016/j.apsb.2020.11.008. Epub 2020 Nov 20.
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--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. cellular uptake results showed that NPs could be internalized into DCs with intact form, and DCs preferred to uptake larger NPs. Consistently, 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.
银屑病是一种自身免疫性炎症性疾病，其中树突状细胞（DCs）在其发病机制中起重要作用。在我们之前的工作中，我们已经证明局部递送载有姜黄素的聚（乳酸-乙醇酸）（PLGA）纳米颗粒（NPs）可以治疗咪喹莫特（IMQ）诱导的银屑病样小鼠。本研究的目的是通过使用荧光探针进一步阐明皮内递送后PLGA NPs的生物命运，包括DCs摄取以及它们在银屑病样小鼠模型中的进一步转运。分别制备了两种尺寸的负载DiO/DiI的PLGA NPs，50±4.9nm（S-NPs）和226±7.8nm（L-NPs）。细胞摄取结果表明，NPs可以完整形式内化到DCs中，并且DCs更喜欢摄取较大的NPs。一致地，研究表明L-NPs被DCs捕获更多，并且在注射8小时后NPs首先被转运到皮肤引流淋巴结（SDLN），然后再转运到脾脏，而更多的S-NPs被转运到SDLN和脾脏。此外，FRET成像显示更多结构完整的L-NPs分布在皮肤和淋巴结中。总之，粒径可以影响皮肤和淋巴系统中DCs对NPs的摄取和转运，这在设计用于治疗银屑病等炎症性皮肤病的NPs时需要考虑。
