Injectable, self-healing and phase change nanocomposite gels loaded with two nanotherapeutic agents for mild-temperature, precise and synergistic photothermal-thermodynamic tumor therapy.

Hyperthermia has emerged as a popular treatment option due to its high efficacy and seamless integration with other therapeutic approaches. To enhance treatment outcomes, hydrogels loaded with photothermal agents and activated by near-infrared (NIR) light for localized tumor therapy have attracted considerable attention. This approach minimizes drug dosage and mitigates the adverse effects of systemic drug delivery on healthy tissues. However, a challenge arises when NIR light sources inadvertently expose hydrogels loaded with high concentrations of photothermal agents, potentially causing localized overheating. Such overheating may trigger issues like inflammation, severe burns, and tissue crusting. To address this issue, the water in traditional hydrogels was substituted with the phase change material poly(ethylene glycol) (PEG), creating a phase change composite gel. This gel utilized PEG 2 M (PEG with a molecular weight of approximately 2,000,000 g/mol) as the gel scaffold and PEG 1.5 K (PEG with a molecular weight of approximately 1,500 g/mol) as the gel medium. Polydopamine modified with folic acid (PDA-FA) and MOF-199 loaded with 2, 2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH@MOF-199) were uniformly dispersed throughout the gel. Experimental results have demonstratedthat this system can extend the duration of photothermal therapy while effectively avoiding localized overheating. Additionally, it synergizes well with thermodynamic therapy.