Simultaneous Diagnosis and Gene Therapy of Immuno-Rejection in Rat Allogeneic Heart Transplantation Model Using a T-Cell-Targeted Theranostic Nanosystem
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- 作者：Yu Guo ; Wenjie Chen ; Weiwei Wang ; Jun Shen ; Ruomi Guo ; Faming Gong ; Shudong Lin ; Du Cheng ; Guihua Chen ; Xintao Shuai
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：December 21, 2012
- 年：2012
- 卷：6
- 期：12
- 页码：10646-10657
- 全文大小：843K
- 年卷期：v.6,no.12(December 21, 2012)
- ISSN：1936-086X
文摘
As the final life-saving treatment option for patients with terminal organ failure, organ transplantation is far from an ideal solution. The concomitant allograft rejection, which is hardly detectable especially in the early acute rejection (AR) period characterized by an intense cellular and humoral attack on donor tissue, greatly affects the graft survival and results in rapid graft loss. Based on a magnetic resonance imaging (MRI)-visible and T-cell-targeted multifunctional polymeric nanocarrier developed in our lab, effective co-delivery of pDNA and superparamagnetic iron oxide nanoparticles into primary T cells expressing CD3 molecular biomarker was confirmed in vitro. In the heart transplanted rat model, this multifunctional nanocarrier showed not only a high efficiency in detecting post-transplantation acute rejection but also a great ability to mediate gene transfection in T cells. Upon intravenous injection of this MRI-visible polyplex of nanocarrier and pDNA, T-cell gathering was detected at the endocardium of the transplanted heart as linear strongly hypointense areas on the MRI T2*-weighted images on the third day after cardiac transplantation. Systematic histological and molecular biology studies demonstrated that the immune response in heart transplanted rats was significantly suppressed upon gene therapy using the polyplex bearing the DGK伪 gene. More excitingly, the therapeutic efficacy was readily monitored by noninvasive MRI during the treatment process. Our results revealed the great potential of the multifunctional nanocarrier as a highly effective imaging tool for real-time and noninvasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.