Department of Pharmaceutical Sciences, Center for Integrated Biotechnology, Washington State University, Pullman, Washington, USA.
Nanomedicine. 2011 Apr;7(2):193-200. doi: 10.1016/j.nano.2010.08.003. Epub 2010 Oct 1.
The objective of this research was to evaluate the efficacy of a recombinant nonviral vector for targeted delivery of a thymidine kinase (TK) suicide gene to xenograft SKOV-3 tumors. The vector was genetically engineered and used to condense the TK gene into particles of less than 100 nm. The nanoparticles were used to transfect and kill SKOV-3 cancer cells in combination with ganciclovir (GCV) in vitro. The results demonstrated that the vector could effectively kill up to 80% of the SKOV-3 cancer cells. In the next step, the ability of the vector to deliver the TK suicide gene to xenograft tumors of SKOV-3 was studied. The results demonstrated that the vector could transfect tumors and result in significant tumor size reduction during the period that GCV was administered. Administration of GCV for at least 3 weeks post transfection was of paramount importance. These results illustrate the therapeutic efficacy and application of a designed recombinant nonviral vector in cancer gene therapy.
A recombinant nonviral vector is used to deliver a suicide thymidine kinase gene under gancylovir control in vitro to SKOV-3 cancer cells with 70% efficiency. Follow on testing in a xenograft tumor demonstrated tumor reduction persisting for three weeks.
本研究的目的是评估一种重组非病毒载体将胸苷激酶（TK）自杀基因靶向递送至异种移植 SKOV-3 肿瘤的疗效。该载体经过基因工程改造，用于将 TK 基因浓缩成小于 100nm 的颗粒。将这些纳米颗粒与更昔洛韦（GCV）联合用于体外转染和杀伤 SKOV-3 癌细胞。结果表明，该载体可有效杀伤高达 80%的 SKOV-3 癌细胞。在下一步，研究了该载体将 TK 自杀基因递送至 SKOV-3 异种移植肿瘤的能力。结果表明，该载体可转染肿瘤，并在给予 GCV 的期间导致肿瘤体积显著缩小。转染后至少 3 周给予 GCV 至关重要。这些结果说明了设计的重组非病毒载体在癌症基因治疗中的治疗效果和应用。
一种重组非病毒载体被用于在体外将一种受更昔洛韦控制的自杀胸苷激酶基因传递至 SKOV-3 癌细胞，效率为 70%。随后在异种移植肿瘤中的测试表明，肿瘤缩小持续了 3 周。
