Dass Crispin R, Contreras Karla G, Dunstan David E, Choong Peter F M
Department of Orthopaedics, University of Melbourne, St. Vincent's Health, P.O. Box 2900, Fitzroy, 3065 Melbourne, Australia.
Biomaterials. 2007 Jul;28(19):3026-33. doi: 10.1016/j.biomaterials.2007.03.016. Epub 2007 Mar 18.
The major stumbling block for most therapies against deep-seated disease, including tumours, is inefficient drug delivery. Such a concern is particularly important for osteosarcoma, the predominant form of bone cancer, and the largest cancer of its type in the paediatric age group. Pigment epithelium-derived factor (PEDF) is the most potent anti-angiogenic factor found endogenously in the body, with an increasing number of reports pointing to its direct antitumour activity. In this report, when a plasmid expressing PEDF (pPEDF) was encapsulated within two types of chitosan microparticles, anti-invasion and increased adhesion of the osteosarcoma cell line SaOS-2 was noted. Microparticles were formulated using two methods of complex coacervation and were approximately 400-600 nm in diameter. The plasmids were strongly attached to the particles which were polymorphic in shape as determined by electron microscopy. Preliminary experiments with the green fluorescent protein (GFP) reporter plasmid revealed that cells were efficiently transfected with the particles, with particles outlasting transfection with lipofectamine cationic liposomes at 5 days. In vivo, the better pPEDF microparticle resulted in a decrease in primary tumour growth, reduced bone lysis and reduced establishment of lung metastases in a clinically relevant orthotopic model of osteosarcoma. Thus, this new mode of localised gene delivery may hold promise for molecular therapy of osteosarcoma.
包括肿瘤在内，大多数针对深部疾病的治疗方法的主要绊脚石是药物递送效率低下。对于骨肉瘤（骨癌的主要形式，也是儿科年龄组中该类型最大的癌症）而言，这种担忧尤为重要。色素上皮衍生因子（PEDF）是体内内源性发现的最有效的抗血管生成因子，越来越多的报告指出其直接抗肿瘤活性。在本报告中，当表达PEDF的质粒（pPEDF）被包裹在两种壳聚糖微粒中时，观察到骨肉瘤细胞系SaOS-2的抗侵袭能力增强和黏附增加。微粒采用两种复凝聚方法制备，直径约为400-600nm。质粒与通过电子显微镜确定为形状多态的颗粒紧密结合。用绿色荧光蛋白（GFP）报告质粒进行的初步实验表明，细胞被微粒有效转染，微粒在5天时的转染持续时间超过脂质体阳离子脂质体。在体内，在骨肉瘤的临床相关原位模型中，更好的pPEDF微粒导致原发性肿瘤生长减少、骨溶解减少和肺转移形成减少。因此，这种新的局部基因递送模式可能为骨肉瘤的分子治疗带来希望。
