Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies

Abstract

Reactive oxygen species (ROS) at supraphysiological concentration have a determinate role in contributing to immuno-metabolic disorders in the epithelial immune microenvironment (EIME) of psoriatic lesions. With an exclusive focus on the gene-oxidative stress environment interaction in the EIME, a comprehensive strategy based on ROS-regulating nanomedicines is greatly anticipated to become the mainstay of anti-psoriasis treatment. This potential therapeutic modality could inhibit the acceleration of psoriasis via remodeling the redox equilibrium and reshaping the EIME. Herein, we present a marked overview of the current progress in the pathomechanisms of psoriasis, with particular concerns on the potential pathogenic role of ROS, which significantly dysregulates redox metabolism of keratinocytes (KCs) and skin-resident or -infiltrating cells. Meanwhile, the emergence of versatile nanomaterial-guided evolution for transdermal drug delivery has been attractive for the percutaneous administration of antipsoriatic therapies in recent years. We emphasize the underlying molecular mechanism of ROS-based nanoreactors for improved therapeutic outcomes against psoriasis and summarize up-to-date progress relating to the advantages and limitations of nanotherapeutic application for transdermal administration, as well as update an insight into potential future directions for nanotherapies in ROS-related skin diseases.

Keywords: Epithelial immune microenvironment; Psoriasis; Reactive oxygen species; Transdermal drug delivery.

Fig. 1

Dysfunctional different cell types (KCs, skin-resident and -infiltrating immune cells function) mediate the propagation of inflammatory loops in EIME of psoriasis: turbulence of EIME evokes the initiation and chronic inflammation in psoriasis significantly associated with oxidative stress. Deleterious reactive metabolites ROS have a harmful role in inducing irreversible damage to these cells in EIME, thereby reprogramming their metabolic pathways involved in the development, proliferation, activation and function. Subsequently, intricately interwoven effects among these cells form clusters of inflammatory circuits in the pathophysiological EIME of cutaneous inflammation, ultimately giving rise to psoriasis

Fig. 2

ROS contributes to the rearranging immunometablism of different cell types, accompanied by exerting their effector functions in response to tissue environments via intermediating the main cellular oxidation-reduction (redox) signaling pathways

Fig. 3

Different types of nanoparticles/nanocarriers used as therapeutic modalities of ROS-related psoriasis

Fig. 4

Ce NPs-based self-therapeutic nanomaterials for the topical treatment of psoriasis. β-cyclodextrin modified ceria nanoparticles were designed as a ROS scavenger nanozyme to transdermal delivery of dithranol for the combinational therapy of psoriasis. Reproduced with permission [178]. Copyright 2020, Dove Medical Press

Fig. 5

Au NPs-based self-therapeutic nanomaterials for the topical treatment of psoriasis. a MTX-GNPs were prepared to inhibit the exacerbation of psoriasis via reshaping the immune infiltration and cytokine secretion of the skin. Reproduced with permission [156]. Copyright 2020, Elsevier. b siRNA conjugated with spherical nucleic acid gold nanoparticles were developed for the reduction of T cell activation and inflammatory gene expression to topically control the progress of psoriasis. Reproduced with permission [182]. Copyright 2017, Elsevier. c Alkyl-terminated Au NPs were synthesized as self-therapeutic nanomedicines for topically preventing and treating imiquimod-induced psoriasis mice via downregulation of gene expression involved in the interleukin-17 signaling pathway. Reproduced with permission [159]. Copyright 2017, American Chemical Society

Fig. 6

Ag NPs-based self-therapeutic nanomaterials for the topical treatment of psoriasis. The Car@NMs@MTX-ZA hydrogel was successfully fabricated as self-therapeutic nanotherapy for combined anti-inflammation with antiproliferation for the treatment of psoriasis. Reproduced with permission [189]. Copyright 2022, Springer Nature

Fig. 7

Polymer-based self-therapeutic nanomaterials for the topical treatment of psoriasis. Cationic nanoparticles were constructed as cfDNA scavengers for topical remission of DNA-LL37-induced cell inflammation in a psoriasiform mice model and cynomolgus monkey model. Reproduced with permission [197]. Copyright 2020, American Association for the Advancement of Science

Fig. 8

Lipid nanomaterials-based transdermal drug delivery platform for the treatment of psoriasis. a The preparation of the DLNP transcutaneous delivery system could improve the skin penetration of STAT3-inhibiting peptides for efficiently treating psoriatic skin inflammation without causing adverse systemic events. Reproduced with permission [153]. Copyright 2018, American Chemical Society. b Hybrid polymer-lipid nanoparticles in combinational with photosensitizer TPPS2a for delivery of siRNA were aimed to topical treat psoriasis effectively through optimizing the endosomal escape of TNFα siRNA in the cytoplasm. Reproduced with permission [208]. Copyright 2021, Elsevier. c Lipid-hybridized CNF film was successfully prepared for transdermal delivery of curcumin to cure psoriasis. Reproduced with permission [206]. Copyright 2018, Elsevier

Fig. 9

Silica nanomaterials-based transdermal drug delivery platform for the treatment of psoriasis. a The synthesis of erianin-loaded dendritic mesoporous silica was employed for topical therapy of psoriasis, ascribed for their mechanisms on pro-apoptotic effect in KCs. Reproduced with permission [203]. Copyright 2020, Springer Nature. b Optimized size of silica NPs decorated with polymer could elevate the affinity of cfDNA to inhibit topical psoriasis inflammation via better penetration ability. Reproduced with permission [157]. Copyright 2021, Elsevier

Fig. 10

Polymer/nanomicelles-based transdermal drug delivery platform for the treatment of psoriasis. Lipid-polymer hybrid nanoparticles were fabricated to load clobetasol propionate for enhancement of its cellular uptake and skin permeability to improve antipsoriatic efficacy. Reproduced with permission [11]. Copyright 2020, Elsevier

Fig. 11

Microneedles-based transdermal drug delivery platform for the treatment of psoriasis. a Microneedle-mediated transdermal codelivery of CRISPR-Cas9–based genome editor and glucocorticoids were used for high-efficiency treatment of psoriasis. Reproduced with permission [168]. Copyright 2021, American Association for the Advancement of Science. b Characterization images of the MN patches, CP/Ad-SS-GD/Cas9 RNP nanoparticles and Dex-loaded PLGA nanoparticles; drug release of Cas9 protein and Dex from the MN patch; fluorescence images of MN patch. Reproduced with permission [168]. Copyright 2021, American Association for the Advancement of Science. c Schematic illustration of the synthesis of SKN-PMs and HCM/SKN-PMs. Reproduced with permission [216]. Copyright 2021, Elsevier. d Sketch of the MN-HCM/SKN-PM preparation process and their characterization images. Reproduced with permission [216]. Copyright 2021, Elsevier

Fig. 12

Hydrogel-based transdermal drug delivery platform for the treatment of psoriasis. a Cur encapsulated into PLGA NPs were synthesized as hydrogel to optimize the dispersion, sustained release and penetration of curcumin across the skin for improvement of its anti-psoriatic efficacy. Reproduced with permission [219]. Copyright 2017, Elsevier. b Therapeutic mechanism of Cel Nio gel for the transcutaneous treatment of imiquimod-induced psoriasiform skin inflammation. Reproduced with permission [221]. Copyright 2021, Dove Medical Press