Manganese-based nanotheranostics synergizing photothermal-chemotherapy for liposarcoma treatment

Liposarcoma (LPS), the most common subtype of soft tissue sarcoma, presents significant therapeutic challenges due to its high heterogeneity, frequent recurrence, and adverse effects on conventional treatments. In this study, we developed multifunctional manganese-based nanotheranostics by integrating Mn₃O₄ nanoparticles (Mn₃O₄ NPs), doxorubicin (DOX), and photosensitizer IR-780, with surface modification using polydopamine (PDA). The manganese-DOX-IR-780 nanoparticles (MDI NPs) exhibited a uniform particle size distribution, excellent colloidal stability, biocompatibility, and pH-responsive drug release capability. Additionally, they achieved efficient photothermal heating, reaching temperatures of 70-80 °C, with a photothermal conversion efficiency (PCE) of 47.6%. Notably, the longitudinal relaxivity of MDI NPs (<i>r</i> ₁ = 1.827 mM^-1 s^-1) was 10.02-fold higher than that of Mn₃O₄ NPs (<i>r</i> ₁ = 0.1824 mM^-1 s^-1), demonstrating its potential as an efficient MRI contrast agent for real-time therapeutic monitoring, with favorable <i>in vivo</i> MRI imaging performance. <i>In vitro</i> experiments revealed that MDI NPs effectively inhibited LPS cell growth with a strong synergistic effect (combination index, CI = 0.17). <i>In vivo</i> studies showed that MDI NPs could accumulate at tumor sites and sustain drug release for over 72 hours. Under mild photothermal conditions (43-45 °C), MDI NPs achieved a remarkable tumor suppression rate of 94.3% and a cure rate of 75%. This study provides a novel, low-toxicity, and highly effective theranostic strategy to overcome the therapeutic challenges of LPS, with significant clinical translation potential.