Yan Lesan, Amirshaghaghi Ahmad, Huang Dennis, Miller Joann, Stein Joel M, Busch Theresa M, Cheng Zhiliang, Tsourkas Andrew
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Adv Funct Mater. 2018 Apr 17;28(16). doi: 10.1002/adfm.201707030. Epub 2018 Feb 15.
The ability to produce nanotherapeutics at large-scale with high drug loading efficiency, high drug loading capacity, high stability, and high potency is critical for clinical translation. However, many nanoparticle-based therapeutics under investigation suffer from complicated synthesis, poor reproducibility, low stability, and high cost. In this work, a simple method for preparing multifunctional nanoparticles is utilized that act as both a contrast agent for magnetic resonance imaging and a photosensitizer for photodynamic therapy for the treatment of cancer. In particular, the photosensitizer protoporphyrin IX (PpIX) is used to solubilize small nanoclusters of superparamagnetic iron oxide nanoparticles (SPIONs) without the use of any additional carrier materials. These nanoclusters are characterized with a high PpIX loading efficiency; a high loading capacity, stable behavior; high potency; and a synthetic approach that is amenable to large-scale production. In vivo studies of photodynamic therapy (PDT) efficacy show that the PpIX-coated SPION nanoclusters lead to a significant reduction in the growth rate of tumors in a syngeneic murine tumor model compared to both free PpIX and PpIX-loaded poly(ethylene glycol)-polycaprolactone micelles, even when injected at 1/8th the dose. These results suggest that the nanoclusters developed in this work can be a promising nanotherapeutic for clinical translation.
能够大规模生产具有高药物负载效率、高药物负载量、高稳定性和高效能的纳米治疗剂对于临床转化至关重要。然而，许多正在研究的基于纳米颗粒的治疗剂存在合成复杂、重现性差、稳定性低和成本高的问题。在这项工作中，利用了一种制备多功能纳米颗粒的简单方法，该纳米颗粒既作为磁共振成像的造影剂，又作为用于癌症治疗的光动力疗法的光敏剂。特别地，光敏剂原卟啉IX（PpIX）用于溶解超顺磁性氧化铁纳米颗粒（SPIONs）的小纳米团簇，而无需使用任何额外的载体材料。这些纳米团簇具有高PpIX负载效率、高负载量、稳定的行为、高效能以及适合大规模生产的合成方法。光动力疗法（PDT）疗效的体内研究表明，与游离PpIX和负载PpIX的聚（乙二醇）-聚己内酯胶束相比，PpIX包覆的SPION纳米团簇在同基因小鼠肿瘤模型中导致肿瘤生长速率显著降低，即使以1/8的剂量注射也是如此。这些结果表明，这项工作中开发的纳米团簇可能是一种有前途的用于临床转化的纳米治疗剂。
