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Hyaluronic Acid–Methotrexate Conjugates Coated Magnetic Polydopamine Nanoparticles for Multimodal Imaging-Guided Multistage Targeted Chemo-Photothermal Therapy

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journal contribution
posted on 16.07.2018, 00:00 by Qi Li, Yilin Chen, Xinyi Zhou, Dengyue Chen, Yang Li, Jiayong Yang, Xuan Zhu
Combination cancer therapy with various kinds of therapeutic approaches could improve the effectiveness of treatment while reducing side effects. Herein, we elaborately developed a theranostics nanoplatform based on magnetic polydopamine (MPDA) coated with hyaluronic acid–methotrexate conjugates (MPDA@HA–MTX) for chemo-photothermal treatment (PTT). In this nanoplatform, Fe3O4 served as the core was applied as contrast agent for T2-weighted magnetic resonance imaging (MRI) and early phase magnet targeting. Meanwhile, PDA was used as a versatile shell for effective loading of chemotherapeutic doxorubicin (DOX) to achieve controlled release and PTT simultaneously. Moreover, HA–MTX conjugates could offer later-phase specific cellular dual-targeting ability during the therapy. Both in vitro and in vivo studies demonstrated that DOX-loaded MPDA@HA–MTX (MPDA/DOX@HA–MTX) exhibited the preferential tumor accumulation, enhanced specificity to target tumor cells, pH-/laser-responsive release, and high tumor cell-killing efficiency. By combined chemo-PTT under the guidance of fluorescence/MR imaging, the tumors in mice were completely eliminated after treatment, indicating that MPDA@HA–MTX nanoparticles have great potential as a novel drug-loading platform for imaging-guided multistage targeted chemo-photothermal combination therapy.