Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, P.R. China.
Nat Commun. 2018 Oct 18;9(1):4335. doi: 10.1038/s41467-018-06574-7.
Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (O) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt)Pt(OTf) as the building block to improve the O QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.
光动力疗法因其微创性、轻微的全身毒性、较少的副作用和避免耐药性而成为传统治疗方法的有效替代方法。然而，由于疏水性光敏剂的严重聚集，设计具有高单线态氧（O）量子产率（QY）的光敏剂仍然具有挑战性。在此，我们使用治疗性顺式-(PEt)Pt(OTf)作为构建块开发了离散的有机铂(II)金属笼，以提高 O QY，从而实现协同抗癌功效。具有三模态成像能力的金属笼负载纳米颗粒（MNPs）可精确诊断肿瘤，并实时监测 MNPs 的递送、分布和排泄。MNPs 表现出优异的抗转移效果和对 U87MG、耐药 A2780CIS 和原位肿瘤模型的优异抗肿瘤性能，单次治疗即可消融肿瘤且无复发。基因芯片分析证实了不同治疗方式对肿瘤消除的贡献。这个超分子平台在精确的癌症治疗中有很大的潜力。
