Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage

Abstract

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO₂ /PDA@Cu, comprising manganese dioxide (MnO₂ ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO₂ /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO₂ /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO₂ /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO₂ and Cu release. The MnO₂ nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO₂ /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

Keywords: cartilage regeneration; multifunctional microneedle; photothermal-controllable; sequential treatment; tracheal neoplasms.