A multifunctional nano-hydrogel attenuates skin photoaging via regulating ECM microenvironment homeostasis

Ultraviolet (UV) radiation exacerbates skin photoaging, disrupting extracellular matrix (ECM) homeostasis and thereby causing premature skin aging and increased susceptibility to damage. Effective therapeutic approaches to manage photoaging and promote skin regeneration are essential. This study developed a multifunctional nanocomposite hydrogel (CAPE@DMMg) by loading active compounds into citrate-functionalized mesoporous silica nanoparticles (CAPE@MSN-CA), incorporating a deep eutectic solvent to enhance skin penetration, and introducing magnesium ions to improve the mechanical stability of the hydrogel. Experimental results demonstrated that CAPE@DMMg scavenged reactive oxygen species, modulated ECM-related gene expression, and reduced skin wrinkles, restores skin thickness, and promotes collagen deposition, exhibiting remarkable anti-photoaging effects. Furthermore, CAPE@DMMg reduced UV-induced senescence-associated markers in multiple organs, indicating reduced systemic oxidative stress and senescence-related changes. Mechanistically, CAPE@MSN-CA restored mitochondrial function by targeting the FN1-ITGA5 axis and suppressing apoptosis. This effect was accompanied by increased type I/III collagen and reduced MMP1 and FN1 expression. In summary, this study presents a multifunctional drug delivery system that regulates ECM microenvironment homeostasis, offering a novel strategy for anti-aging skin therapy.