Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
Drug Deliv. 2012 Sep-Oct;19(7):317-26. doi: 10.3109/10717544.2012.714809. Epub 2012 Sep 18.
Chemotherapy in treatment of malignant tumors has many side effects due to the poor physiochemical properties and the toxicity to normal tissues. The dual-targeting drug delivery system combining two high-affinity ligands can target anticancer drug primary to the diseased tissue, then to the tumor, which provides both greater efficacy of treatment and less harm to normal tissues. In this paper, a novel dual-targeting moiety RGD(7) (R-G-D-D-D-D-D-D-D; Nonapeptide for bone cancer combining D(6) peptide as bone target moiety and RGD peptide as tumors target moiety was contracted. A series of bone and/or tumor targeting conjugates have been synthesized in a convergent approach and well characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The hydroxyapatite (HAP) binding, water solubility, the drug release and the distribution in vivo were evaluated. All the conjugates were water-soluble and able to release the parent drugs in vitro. The bone-targeting property of the dual-targeting delivery system was enhanced from the results of the HAP binding and the distribution in vivo. The experiment for verifying tumor targeting property was underway. These results provided an effective entry to the development of a new dual-targeting delivery system for bone cancer.
化疗在治疗恶性肿瘤方面有许多副作用，这是由于其较差的物理化学性质和对正常组织的毒性。结合两种高亲和力配体的双靶向药物传递系统可以将抗癌药物靶向到病变组织，然后靶向到肿瘤，从而提供更高的治疗效果和更少的对正常组织的伤害。本文设计了一种新型双靶向 RGD（7）（R-G-D-D-D-D-D-D-D；将 D（6）肽作为骨靶向基团和 RGD 肽作为肿瘤靶向基团的九肽）。采用收敛法合成了一系列骨和/或肿瘤靶向缀合物，并通过核磁共振（NMR）和质谱（MS）技术对其进行了很好的表征。评估了羟磷灰石（HAP）结合、水溶性、药物释放和体内分布。所有缀合物均为水溶性，能够在体外释放母体药物。从 HAP 结合和体内分布的结果可以看出，双靶向递药系统的骨靶向性得到了增强。验证肿瘤靶向性的实验正在进行中。这些结果为开发用于骨癌的新型双靶向递药系统提供了有效途径。
