A DNA nanoflowers-based microneedle patch for transdermal gene and photodynamic therapy against melanoma

DNA nanostructures show great potential as drug carriers in biomedicine, however, biological barriers and stability issues limit their applications, particularly for aggressive melanoma shielded by the skin barrier. This study presents a hyaluronic acid-based microneedle patch integrated with DNA nanoflowers to effectively penetrate the skin barrier. The DNA nanoflowers (Z/H@DFs) are self-assembled from PD-L1 antisense oligonucleotide (ASO), AS1411 G-quadruplex units, Hemin, and ZnPc. In a B16F10 melanoma mouse model, the Z/H@DFs-based microneedle patches (Z/H@DFMNs) significantly inhibited tumor growth. Mechanistically, Z/H@DFMNs patch relieved hypoxia, promoted the photodynamic therapy effect, and activated anti-tumor immunity via the suppression of PD-L1 expression. The proposed synergistic photo-immunotherapy strategy could realize 3-fold enhancement in tumor infiltrating CD8⁺ T cells and over 2-fold increase in serum IFN-γ and TNF-α levels. The Z/H@DFMNs patch is a potential solution for melanoma immunome and other skin disorders.