Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China.
Biomaterials. 2012 Sep;33(26):6155-61. doi: 10.1016/j.biomaterials.2012.05.035. Epub 2012 Jun 8.
A nanopharmaceutical system using TAT-enhanced cell/tissue penetration strategy was developed for multidrug-resistant (MDR) cancer treatment, in which nanocrystalline silver with mean size of 8 nm modified with TAT cell-penetrating peptide (termed AgNP-TAT) displayed extraordinary antitumor activity in both MDR cells and non-resistant cells at an indiscriminating manner. Such anti-MDR effect is presumably due to the size-exclusion effect, by which the nanoparticles are too large to be pumped out. Of note, AgNP-TAT showed significant enhancement in killing tumor cells, e.g. up to 24 fold higher compared to its counterpart without TAT-modification. The animal studies further confirmed the success of our strategy that AgNP-TAT was able to effectively inhibit the tumor growth in the mice bearing malignant melanoma at a dose of 1 nmol/kg, compared with the effective dose (4.3 μmol/kg) of doxorubicin. AgNP-TAT also showed significantly reduced adverse toxicity in vivo. It indicates AgNP-TAT could be a class of nano drug for MDR cancer treatment.
一种使用 TAT 增强的细胞/组织穿透策略的纳米制药系统被开发用于多药耐药（MDR）癌症治疗，其中用 TAT 细胞穿透肽修饰的平均尺寸为 8nm 的纳米晶银（称为 AgNP-TAT）以一种不分青红皂白的方式在 MDR 细胞和非耐药细胞中表现出非凡的抗肿瘤活性。这种抗 MDR 作用可能归因于尺寸排除效应，通过该效应，纳米颗粒太大而无法被泵出。值得注意的是，AgNP-TAT 在杀死肿瘤细胞方面表现出显著的增强作用，例如，与没有 TAT 修饰的 AgNP-TAT 相比，其增强作用高达 24 倍。动物研究进一步证实了我们的策略的成功，即 AgNP-TAT 能够以 1nmol/kg 的剂量有效抑制携带恶性黑色素瘤的小鼠的肿瘤生长，而阿霉素的有效剂量（4.3μmol/kg）。AgNP-TAT 在体内也表现出显著降低的不良反应毒性。这表明 AgNP-TAT 可以成为一类用于治疗 MDR 癌症的纳米药物。
