Tumor Theranostics of Transition Metal Ions Loaded Polyaminopyrrole Nanoparticles

载有过渡金属离子的聚氨基吡咯纳米粒子的肿瘤诊疗

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Abstract

Polypyrrole (PPy) nanoparticles (NPs) possess high near-infrared absorption and good biosafety, showing the potentials as photothermal therapeutic materials. However, the single function and the weak diagnostic function limit the further combination with other functional units to achieve theranostics. In this work, polyaminopyrrole (PPy-NH(2)) is demonstrated as the alternative of PPy for preparing NPs. Because of the amino group, metal ions, such as Cu(II) and Fe(III) can be loaded in PPy-NH(2) NPs, which extends the applications in multimodal theranostics. Systematical studies reveal that the contribution of Cu(II) in multimodal theranostics is greater than Fe(III). Cu can enhance T(1) response signal for magnetic resonance imaging (MRI) and be released controllably in the organism, leading to the effect of chemotherapy. Therefore, Cu(II) and Fe(III) co-loaded PPy-NH(2) NPs are defined as CuPPy-NH(2) NPs. Experimental results indicate that the optimal size of CuPPy-NH(2) NPs is 50.2 nm. The photothermal transduction efficiency is 76.4%. After thermochemotherapy, a complete ablation of human oral epithelial carcinoma tumors is observed. No tumor recurrence is found. Methods: Cu(II) and Fe(III) co-loaded PPy-NH(2) NPs are prepared through oxidation polymerization by mixing Py-NH(2), CuCl(2), and FeCl(3) in water under stirring at room temperature, which are defined as CuPPy-NH(2) NPs. The as-prepared CuPPy-NH(2) NPs are tested with a variety of cell and animal experiments for tumor theranostics. Results: CuPPy-NH(2) NPs have good light stability, photothermal stability, biosafety and low toxicity. The optimal size of theranostic CuPPy-NH(2) NPs is 50.2 nm, which present a photothermal transduction efficiency of 76.4%. The doped Cu(II) ions also show chemotherapeutic behavior. After thermochemotherapy, a complete ablation of human oral epithelial carcinoma tumors is observed. No tumor recurrence is found. Because of the unpaired electron in Cu atomic orbits, CuPPy-NH(2) NPs also show T(1)-weighted magnetic resonance imaging. Conclusions: This kind of transition metal-doped polymer gives a competitive approach for designing and fabricating multimodal theranostic nanodevices, which shows the potential in tumor treatment.

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