Cu²⁺-Loaded Polydopamine Nanoparticles for Magnetic Resonance Imaging-Guided pH- and Near-Infrared-Light-Stimulated Thermochemotherapy

Cancer multimodal treatment by combining the effects of different theranostics agents can efficiently improve treatment efficacy and reduce side effects. In this work, we demonstrate the theranostics nanodevices on the basis of Cu²⁺-loaded polydopamine nanoparticles (CuPDA NPs), which are able to offer magnetic resonance imaging (MRI)-guided thermochemotherapy (TCT). Systematical studies reveal that after Cu²⁺ ions loading, the molar extinction coefficient of PDA NPs is greatly enhanced by 4 times, thus improving the performance in photothermal therapy. Despite Cu²⁺ ions being toxic, the release of Cu²⁺ is mainly stimulated in acidic environment. Once the NPs deposit in the slightly acidic tumor microenvironment (pH ≈ 6.5–6.8), the release rate boosts ∼30%, which effectively avoids the systematic toxicity during chemotherapy. Meanwhile, due to the increment of the electron–proton dipole–dipole interaction correlation time τ_C, the spin–lattice relaxation time (T₁) for PDA NPs is found to be shortened by Cu²⁺ loading, which boosts the longitudinal relaxivity (r₁). Hence, CuPDA NPs can be used as T₁-weighted contrast agent in MRI. In addition, due to the naturally existing DA in the human body with stealth effect, CuPDA NPs have an outstanding tumor retention rate as high as 8.2% ID/g. Further in vitro and in vivo tests indicate that CuPDA NPs possess long blood circulation time, good photothermal and physiological stability, and biocompatibility, which are potential nanodevices for MRI-guided TCT with minimal side effects.