Soluble hyaluronic acid microneedle arrays mediated RGD-modified liposome delivery for pain relief during photodynamic therapy by blocking TRPV1

In photodynamic therapy (PDT), reactive oxygen species (ROS) are key products that induce cell death, and increasing amount of ROS is a crucial way to enhance PDT efficacy. However, the generated ROS stimulates the transient receptor potential vanilloid 1 channel (TRPV1), which can be activated in the pain pathway and then exacerbate pain. Herein, we utilized arginine−glycine−aspartate (RGD) peptide-modified liposomes for encapsulation Chlorin e6 (Ce6) and capsazepine (Cz), a receptor antagonist of TRPV1, to prepare drug-loaded liposomes, RLCC. Soluble hyaluronic acid microneedle arrays (MNs), which possess sufficient skin penetration capability and excellent biosafety, was applied for in situ delivery of RLCC. With the aid of RGD peptides, the efficiency of intracellular liposomal uptake and the dispersion of drugs in tumor after delivery by MNs were significantly enhanced, showcasing tremendous potential for improving the PDT efficacy. Besides, through the analysis of sciatic nerve signals in mice during PDT, RLCC demonstrated remarkable effectiveness in alleviating pain by significantly reducing nerve impulses. Hence, RLCC demonstrated outstanding effectiveness in PDT and effectively alleviated the associated pain. Overall, this research highlights the potential of utilizing MNs for the in situ delivery of RLCC, facilitating effective PDT while addressing the issue of pain during the treatment.