Recent advances in gene therapy-based cancer monotherapy and synergistic bimodal therapy using upconversion nanoparticles: Structural and biological aspects.

In accordance with human genetics and genomics advances over the past years, it can be found that cancer is created through a somatic aberration in the host genome. Accordingly, researchers use therapeutic methods in genetic manipulation to discover the possible cure for the disease. In combination with traditional cancer treatments, gene therapy (GT) is essential in future cancer therapy. The development of powerful nanocarriers for targeted, controlled, and efficient intracellular delivery of therapeutic biomolecules that increase pharmacokinetics indicates that the development of GT is highly dependent on nanotechnology. Among nanocarriers, upconversion nanoparticles (UCNPs) have become the focus of great attention in the realm of inorganic nanomedicines following the strategy of "diagnosis for treatment" due to their outstanding features including safety, deep penetration of near-infrared (NIR) light into tissue, and reduction of unfavorable side effects of NIR-triggered therapies. Moreover, various individual therapies can be intelligently combined into a single nanotranostic system based on a UCNP platform for multimodal synergistic treatment. Given that the preparation of multifunctional nanomaterials is a prerequisite for the realization of cancer treatment, especially synergistic therapies, the recognition of the main components of advanced nanoparticles can help researchers in choosing the proper platform for cancer treatment. In view of this, the main goal of this review is to highlight the latest advances in the construction and application of upconversion nanoparticles as carriers for gene delivery and gene editing in cancer monotherapy and bimodal synergistic therapy, with an emphasis on the structural and biological aspects of these studies.