Implantable Light Source‐Integrated Microneedles for Losartan‐Enhanced and Sustained Photodynamic Therapy of Tumors

Abstract Conventional photodynamic therapy (cPDT), which typically delivers intermittent light irradiation to the tumor site, faces several limitations, including time/location constraints, poor patient compliance, inadequate light penetration depth, hypoxic tumor microenvironments (TME), and fibrotic barriers, which collectively compromise its therapeutic efficacy. To address these challenges, an implantable microneedle‐based sustained photodynamic therapy (sPDT) strategy for treating tumors is proposed, using light source‐embedded microneedles (MNs) that can provide continuously release of losartan, enabling four synergistic functions: a wearable wireless light‐emitting diode overcomes the spatiotemporal constraints of cPDT; administrate a complex of a fluorinated, degradable polycationic SS‐HPT‐F, and pCAT‐KR, a plasmid which can express catalase and KillerRed (KR) in the same cell, to alleviate tumor hypoxia exacerbated by prolonged light irradiation; in situ implantation of light‐integrated MNs resolves light penetration depth inadequacies; and local continuously release of losartan through MN cavities bypasses systemic toxicity from intravenous administration and enhances tumor penetration hindered by fibrotic barriers. In vivo studies demonstrate that this sPDT strategy significantly enhances tumor SS‐HPT‐F/pCAT‐KR penetration while suppressing tumor fibrosis and hypoxic conditions in TME, achieving superior therapeutic efficacy over cPDT. This study not only addresses intratumoral drug penetration and accumulation but also provides new insights for advancing photodynamic therapy.