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

• Published in: Acta pharmaceutica Sinica. B Vol. 11; no. 4; pp. 1047 - 1055
• Main Authors: Lin, Zibei, Xi, Long, Chen, Shaokui, Tao, Jinsong, Wang, Yan, Chen, Xin, Li, Ping, Wang, Zhenping, Zheng, Ying
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2021; Elsevier
• Subjects: Biofate; Dendritic cells; Fluorescence; Fluorescence resonance energy transfer; Lymphoid organs; Original; PLGA nanoparticles; Psoriasis; Uptake and trafficking; Biofate; Uptake and trafficking; APCs; Psoriasis; Dendritic cells; DiI; Fluorescence; PFA; DiO; MLN; NPs; PDI; DCs; SDLN; Lymphoid organs; Fluorescence resonance energy transfer; CLSM; DMF; PLGA nanoparticles; DiI, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; DCs, dendritic cells; DiO, 3,3′-dioctadecyloxacarbocyanine perchlorate; MLN, mesenteric lymph nodes; CLSM, confocal laser scanning microscope; APCs, antigen-presenting cells; PDI, polydispersity index; SDLN, skin-draining lymph nodes; DMF, dimethylformamide; PFA, paraformaldehyde; NPs, nanoparticles
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2020.11.008

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. Schematic illustration of uptake and trafficking of two particle-sized PLGA nanoparticles (NPs) in IMQ-induced psoriasis-like mice. Compared to L-NPs, more S-NPs were transported to skin-draining lymph nodes (SDLN) and spleens after intradermal injection. And dendritic cells preferred to uptake L-NPs both in vitro and in vivo. [Display omitted]