NIR-Responsive CoSn(OH)6/CuS Heterostructure Microneedles Integrate ROS and H2S Generation with Tanshinone IIA Delivery for Breast Cancer Therapy

Abstract

Coordinating catalytic species, gaseous mediators, and small-molecule drugs at a tumor site remains difficult because each component follows a different activation and release process. To address this challenge, we constructed oxygen-vacancy-enriched hollow CoSn(OH)6/CuS heterostructures (CC) by alkaline etching and subsequent in situ hydrothermal deposition of CuS, and coloaded CC with tanshinone IIA (Tan-IIA) to form CCT; this formulation was then incorporated into a photothermally responsive PCL/PVP microneedle patch, denoted CCT-MN. Hollowing the CoSn(OH)6 cubes increased surface accessibility, whereas interfacial CuS growth extended near-infrared (NIR) absorption, promoted charge transfer, and strengthened photothermal conversion. Upon 808-nm exposure, a CC dispersion reached approximately 54 °C, afforded a photothermal conversion efficiency of 20.8%, and retained its heating performance during repeated irradiation cycles. The vacancy-rich heterostructure promoted singlet-oxygen production; under acidic conditions, Cu2+ sites catalyzed Fenton-like hydroxyl-radical formation, while protonation of sulfide species supplied H2S. The optimized patch possessed intact and mechanically robust needles, penetrated a skin-mimicking hydrogel, dissolved faster under laser heating, and promoted simultaneous H2S generation and Tan-IIA release in response to acidity and NIR irradiation. In 4T1 cells, the laser-activated CCT formulation increased ROS and H2S levels, disrupted lysosomes, collapsed the mitochondrial membrane potential, and caused extensive cell death. In tumor-bearing mice, CCT-MN irradiation increased the tumor-surface temperature from 38.5 to 56.5 °C and achieved the greatest tumor suppression among the tested regimens, without detectable weight loss or histological injury to major organs. These findings establish a locally implanted heterostructure microneedle system that synchronizes photothermal, photodynamic, chemodynamic, gas, and Tan-IIA-assisted antitumor actions.