Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

Abstract

Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

Bacterial vectors for imaging and cancer gene therapy: a review

“…The high level of autofluorescence and visible light absorption associated with in vivo imaging of fluorophores in the green spectrum greatly limits the tissue depth from which a clear fluorescent signal can be obtained. 54,55 However, the development of near-infrared (NIR) probes has allowed the in vivo analysis of fluorescence to become practical. 56 NIR probes reduce the level of background signal by increasing the signal-to-noise ratio and therefore facilitates fluorescent imaging at greater depths.…”

Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA

“…However, there are major limitations of the use of siRNA as a therapeutic tool, including its degradation by extracellular nucleases and poor cellular uptake. Although a number of vehicles, such as cationic liposomes, viral vectors and nanoparticles, have been used to transport siRNA, there are disadvantages of each method . Therefore, it remains a challenge to deliver interfering RNA to tumor cells in vivo.…”

Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos

“…Dual modification of lambda phage for targeted delivery of genes of interest to the immune system is a promising method for combating various diseases. The surface of the lambda phage displays specific ligands and the capsid encapsulates the selected gene sequence that is protected from degradation by enzymes[97]. Thoma et al[98] also confirmed that this strategy could produce higher immune response in the absence of any adjuvant and at physiological pH.…”