Department of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Biomaterials. 2012 Oct;33(29):7164-73. doi: 10.1016/j.biomaterials.2012.06.026. Epub 2012 Jul 12.
Delivery of therapeutic agents to bone is crucial in several diseases such as osteoporosis, Paget's disease, myeloproliferative diseases, multiple myeloma as well as skeletal metastasizing cancers. Prevention of cancer growth and lowering the cancer induced bone resorption is important in the treatment of bone metastasizing cancers. Keeping in mind the low diffusivity and availability of cell surface targets on cancer cells, we designed a targeted system to deliver chemotherapeutic agents to the bone microenvironment as an approach to tissue targeting using alendronate (Aln). We co-encapsulated curcumin and bortezomib in the PLGA nanoparticles to further enhance the therapeutic efficiency and overall clinical outcome. These multifunctional nanoparticles were characterized for particle size, morphology and drug encapsulation. The particles were spherical with smooth surface and had particle size of 235 ± 70.30 nm. We validated the bone targeting ability of these nanoparticles in vitro. Curcumin and bortezomib are known to have synergistic effect in inhibition of growth of cancer; however there was no synergism in the anti-osteoclastogenic activity of these agents. Surprisingly, curcumin by itself had significant inhibition of osteclastogenic activity. In vivo non-invasive bioimaging showed higher localization of Aln-coated nanoparticles to the bone compared to control groups, which was further confirmed by histological analysis. Aln-coated nanoparticles protected bone resorption and decreased the rate of tumor growth as compared to control groups in an intraosseous model of bone metastasis. Our data show efficient attachment of Aln on the surface of nanoparticles which could be used as a drug carrier for preferential delivery of multiple therapeutic agents to bone microenvironment.
将治疗剂递送到骨骼对于多种疾病至关重要，如骨质疏松症、佩吉特病、骨髓增生性疾病、多发性骨髓瘤以及骨骼转移性癌症。预防癌症生长和降低癌症引起的骨质吸收对于治疗骨骼转移性癌症非常重要。考虑到癌细胞表面靶标扩散性低和可用性低，我们设计了一种靶向系统，将化疗药物递送到骨微环境中，作为利用阿仑膦酸盐（Aln）进行组织靶向的方法。我们将姜黄素和硼替佐米共包封在 PLGA 纳米粒子中，以进一步提高治疗效率和整体临床效果。这些多功能纳米粒子的粒径、形态和药物包封进行了表征。这些粒子呈球形，表面光滑，粒径为 235±70.30nm。我们在体外验证了这些纳米粒子的骨靶向能力。姜黄素和硼替佐米在抑制癌细胞生长方面具有协同作用；然而，这些药物在抗破骨细胞生成活性方面没有协同作用。令人惊讶的是，姜黄素本身对破骨细胞生成活性有显著抑制作用。体内非侵入性生物成像显示，与对照组相比，阿仑膦酸盐涂层纳米粒子更能定位于骨骼，组织学分析进一步证实了这一点。与对照组相比，阿仑膦酸盐涂层纳米粒子在骨转移的骨内模型中能保护骨质吸收并降低肿瘤生长速度。我们的数据表明，阿仑膦酸盐能有效地附着在纳米粒子的表面上，可作为一种药物载体，将多种治疗剂优先递送到骨微环境中。
