Uptake and traffcking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

摘要

Psoriasis is an autoimmune infammatory 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 traffcking in psoriasis-like mice model by using fuorescence 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 frstly transported to skindraining 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 traffcking of NPs by DCs in skin and lymphoid system,which needs to be considered in NPs tailing to treat infammatory skin disease like psoriasis.