Atopic dermatitis (AD), a chronic inflammatory skin disorder, remains a major therapeutic challenge in clinical practice. Its pathogenesis is primarily driven by dysregulated T helper 2 (Th2) immune responses and pathological accumulation of reactive oxygen species (ROS). Here, we demonstrated that Portulaca oleracea L.-derived exosome-like nanoparticles (PELNs) exerted potent anti-inflammatory effects on skin-associated cells. However, PELNs have limited antioxidant activity and poor skin barrier penetration. To address these limitations, we developed a dissolvable microneedle (MN) patch incorporating 4-amino-2,2,6,6-tetramethylpiperidinyloxy (4-amino-TEMPO) conjugated with hyaluronic acid (HA-TEMPO) as both an ROS-scavenging agent and a needle-forming matrix, combined with PELN for synergistic therapy. In vivo studies showed that this MN system (designated HA-TEMPO@PELN-MN) effectively attenuated cutaneous oxidative stress and suppressed pathological skin crusting. Notably, the HA-TEMPO@PELN-MN restored Th1/Th2 immune balance. Overall, the MN patch combines excellent biocompatibility, rapid drug release, and efficient delivery, offering a safe and controlled strategy for AD treatment.

Psoriasis is a chronic skin disease characterized by the hyperproliferation of keratinocytes and an overactive autoimmune response. Photodynamic therapy (PDT) has been established as a promising intervention for alleviating psoriasis. However, the current transdermal delivery of photosensitizers is inefficient and imprecise. In this study, we developed a foamed microemulsion nanodroplets system containing chlorin e6 (Ce6 FM), exhibiting precise epidermal targeting and retention, which targeted the aberrantly proliferating epidermal cells at psoriatic skin lesions and avoided the damage to the normal cutaneous cells. Upon application in a psoriatic mouse model, Ce6 FM efficiently induced keratinocyte apoptosis by generating reactive oxygen species under laser. Furthermore, Ce6 FM-based PDT activated the cyclooxygenase-2-induced immunosuppressive pathway in keratinocytes, resulting in the amelioration of the autoimmune microenvironment in psoriatic skin. Additionally, Ce6 FM-based PDT did not induce skin damage or atrophy associated with non-targeted halometasone treatment. Overall, Ce6 FM-based PDT holds promise as an effective, safe and compliant strategy for psoriasis treatment.

Exosomes make a significant contribution during stem cell-based therapy due to the abundant contents. Accumulating evidence implies exosomes can act as potential biological nano agents. We herein propose hypoxic preconditioning for neural stem cells (NSCs) that could produce hypoxic exosomes for efficient treatment of ischemic stroke. Hypoxic preconditioning on NSCs significantly altered the miRNAs encapsulated in exosomes. Notably, hypoxic exosomes could target the injured brain to regulate the microenvironment to inhibit neuroinflammation and promote blood–brain barrier permeability recovery. Additionally, the autologous NSCs in Nestin-CreER mice could be activated by hypoxic exosomes to facilitate nerve regeneration. After hypoxic preconditioning, exosomes further exerted therapeutic effects on both survival (25%) and behavioral outcomes in ischemic stroke mice. Overall, hypoxic preconditioning NSCs can produce effective nano agent and may represent a promising strategy for clinical neurorestorative therapy.