Objective To preliminary study on the physical properties of HN- 1 modified adriamycin (DOX) nanoparticle system HPD and to prove its transplanted oral squamous cell carcinoma (OSCC)-targeting capability. Methods Firstly, the targeting capability of HN-1 for OSCC cells was verified. PEGylated DOX (PD) nanoparticles were synthesized by self-assembly in aqueous media. HN-1 was then chemically grafted onto the surface of PD nanoparticles to form HPD nanoparticles. The HPD nanoparticles were stored in H2O, PBS and PBS containing 10%serum for different time periods. The sizes and distribution diagrams of nanoparticles were evaluated at 1, 3, 5 and 7 days. The serum levels of DOX mediated by HPD nanoparticles were measured. The stability of HPD nanoparticles in vivo was studied. The tumor bearing mice were prepared by inoculating 2.0 × 106 SCC-25 cells into BALB/C nude mice. Then, mice were randomly divided into four groups (n=2 for each group), normal saline group (control), free DOX group, PD group and HPD nanoparticle group. A dose of 8.0 mg/kg body weight on a DOX basis was injected intravenously though tail vain. The mice were sacrificed at 8 h and 24 h after injection, and the major organs (heart, liver, spleen, lung and kidney) and tumor were excised. The ex vivo DOX fluorescence imaging was obtained using the IVIS. Results HN-1 showed strong capability of targeting OSCC cells. HPD nanoparticles showed an uniform spherical shape and a small size of 150 nm, which also showed strong stability. In the nude mice bearing OSCC tumor, HPD nanoparticles displayed remarkably enhanced tumor-targeting and penetrating efficiency compared with those of PD nanoparticles. Conclusion This study demonstrates that HPD nanoparticles mediated by HN-1 can efficiently target transplanted OSCC, and have potential application for the OSCC-targeting treatment.%目的 初步研究HN-1修饰的阿霉素(DOX)纳米颗粒HPD的物理性质及其对口腔鳞癌(OSCC)移植瘤的靶向性.方法 首先验证HN-1在细胞水平对OSCC的靶向性,然后应用改良的纳米沉淀法制备PD纳米颗粒,并在其表面修饰HN-1以制备具有特异靶向性的HPD纳米颗粒.将HPD纳米颗粒溶液分别用H2O、PBS和含10%血清的PBS稀释保存,并于第1、3、5、7天分别测量其粒径大小和分布.测定大鼠体内HPD纳米颗粒介导的DOX的血清浓度变化,研究其在大鼠体内的稳定性.构建裸鼠OSCC移植瘤模型,然后随机数字表法将其平均分为4组,每组2只,分别是生理盐水组(空白对照组),游离DOX组,PD和HPD纳米颗粒组,经尾静脉给予等体积的生理盐水、游离DOX、PD和HPD纳米颗粒溶液,其中给药各组DOX剂量均为8.0 mg/kg,给药后8 h和24 h处死各组小鼠,并取出其肿瘤组织和主要器官(心、肝、脾、肺和肾),通过小鼠各部位荧光强度分布,分析HPD纳米颗粒的靶向性及其组织分布.结果 游离HN-1对OSCC细胞具有较强的靶向性;HN-1修饰的HPD纳米颗粒形貌规则,粒径均一,约150 nm大小;HPD纳米颗粒在体内外具有较好的稳定性,比PD纳米颗粒显示出更强的肿瘤靶向性和渗透性.结论 由HN-1修饰的HPD纳米颗粒对OSCC移植瘤具有较好的靶向性,对于靶向治疗OSCC有应用前景.
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