State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University , Changchun 130012, People's Republic of China.
Department of Oral Pathology, School and Hospital of Stomatology, Jilin University , Changchun 130021, People's Republic of China.
ACS Appl Mater Interfaces. 2017 Jun 14;9(23):19706-19716. doi: 10.1021/acsami.7b05583. Epub 2017 Jun 5.
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 Cu-loaded polydopamine nanoparticles (CuPDA NPs), which are able to offer magnetic resonance imaging (MRI)-guided thermochemotherapy (TCT). Systematical studies reveal that after Cu ions loading, the molar extinction coefficient of PDA NPs is greatly enhanced by 4 times, thus improving the performance in photothermal therapy. Despite Cu ions being toxic, the release of Cu 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, the spin-lattice relaxation time (T) for PDA NPs is found to be shortened by Cu loading, which boosts the longitudinal relaxivity (r). Hence, CuPDA NPs can be used as T-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.
通过结合不同治疗试剂的效果进行癌症多模态治疗可以有效地提高治疗效果并降低副作用。在这项工作中，我们展示了基于负载铜的聚多巴胺纳米粒子（CuPDA NPs）的治疗诊断纳米器件，其能够提供磁共振成像（MRI）引导的热化疗（TCT）。系统研究表明，负载 Cu 离子后，PDA NPs 的摩尔消光系数大大提高了 4 倍，从而提高了光热治疗的性能。尽管 Cu 离子具有毒性，但 Cu 的释放主要是在酸性环境中受到刺激。一旦 NPs 沉积在略酸性的肿瘤微环境（pH ≈ 6.5-6.8）中，释放速率就会提高约 30%，这有效地避免了化疗过程中的系统性毒性。同时，由于电子-质子偶极-偶极相互作用相关时间 τ 的增加，负载 Cu 后 PDA NPs 的自旋晶格弛豫时间（T）被发现缩短，从而提高了纵向弛豫率（r）。因此，CuPDA NPs 可用作 MRI 的 T 加权造影剂。此外，由于人体中天然存在具有隐身效应的 DA，CuPDA NPs 具有高达 8.2% ID/g 的出色肿瘤保留率。进一步的体外和体内试验表明，CuPDA NPs 具有较长的血液循环时间、良好的光热和生理稳定性以及生物相容性，是用于 MRI 引导 TCT 的潜在纳米器件，副作用极小。
