State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China.
ACS Nano. 2010 Oct 26;4(10):5573-84. doi: 10.1021/nn1005599.
Biodegradable cationic nanoparticles have promising application as a gene delivery system. In this article, heparin-polyethyleneimine (HPEI) nanogels were prepared, and these nanogels were developed as a nonviral gene vector. The transfection efficiency of HPEI nanogels was comparable with that of PEI25K, while the cytotoxicity was lower than that of PEI2K and much lower than that of PEI25K in vitro. These HPEI nanogels also had better blood compatibility than PEI25K. After intravenous administration, HPEI nanogels degraded, and the degradation products were excreted through urine. The plasmid expressing vesicular stomatitis virus matrix protein (pVSVMP) could be efficiently transfected into C-26 colon carcinoma cells by HPEI nanogels in vitro, inhibiting the cell proliferation through apoptosis induction. Intraperitoneal injection of pVSVMP/HPEI complexes efficiently inhibited the abdominal metastases of C-26 colon carcinoma through apoptosis induction (mean tumor weight in mice treated with pVSVMP/HPEI complex = 0.93 g and in control mice = 3.28 g, difference = 2.35 g, 95% confidence interval [CI] = 1.75-2.95 g, P < 0.001) and prolonged the survival of treated mice. Moreover, intravenous application of pVSVMP/HPEI complexes also inhibited the growth of pulmonary metastases of C-26 colon carcinoma through apoptosis induction. The HPEI nanogels delivering pVSVMP have promising application in treating colon carcinoma.
可生物降解的阳离子纳米颗粒有望作为基因传递系统得到应用。在本文中，制备了肝素-聚乙烯亚胺（HPEI）纳米凝胶，并将其开发为非病毒基因载体。HPEI 纳米凝胶的转染效率可与 25kDa 的聚乙烯亚胺（PEI25K）相媲美，而体外细胞毒性则低于 2kDa 的聚乙烯亚胺（PEI2K）和 25kDa 的聚乙烯亚胺（PEI25K）。与 PEI25K 相比，这些 HPEI 纳米凝胶还具有更好的血液相容性。静脉给药后，HPEI 纳米凝胶降解，降解产物通过尿液排出。表达水疱性口炎病毒基质蛋白（pVSVMP）的质粒可通过 HPEI 纳米凝胶在体外有效地转染 C-26 结肠癌细胞，通过诱导细胞凋亡抑制细胞增殖。通过诱导细胞凋亡，腹腔内注射 pVSVMP/HPEI 复合物可有效抑制 C-26 结肠癌细胞的腹腔转移（用 pVSVMP/HPEI 复合物处理的小鼠的平均肿瘤重量为 0.93g，对照组小鼠的平均肿瘤重量为 3.28g，差值为 2.35g，95%置信区间[CI]为 1.75-2.95g，P<0.001），并延长了治疗小鼠的存活时间。此外，静脉应用 pVSVMP/HPEI 复合物也可通过诱导细胞凋亡抑制 C-26 结肠癌细胞的肺转移。携带 pVSVMP 的 HPEI 纳米凝胶在治疗结肠癌方面具有广阔的应用前景。
