Joining Forces: The Combined Application of Therapeutic Viruses and Nanomaterials in Cancer Therapy

Abstract

Cancer, on a global scale, presents a monumental challenge to our healthcare systems, posing a significant threat to human health. Despite the considerable progress we have made in the diagnosis and treatment of cancer, realizing precision cancer therapy, reducing side effects, and enhancing efficacy remain daunting tasks. Fortunately, the emergence of therapeutic viruses and nanomaterials provides new possibilities for tackling these issues. Therapeutic viruses possess the ability to accurately locate and attack tumor cells, while nanomaterials serve as efficient drug carriers, delivering medication precisely to tumor tissues. The synergy of these two elements has led to a novel approach to cancer treatment-the combination of therapeutic viruses and nanomaterials. This advantageous combination has overcome the limitations associated with the side effects of oncolytic viruses and the insufficient tumoricidal capacity of nanomedicines, enabling the oncolytic viruses to more effectively breach the tumor's immune barrier. It focuses on the lesion site and even allows for real-time monitoring of the distribution of therapeutic viruses and drug release, achieving a synergistic effect. This article comprehensively explores the application of therapeutic viruses and nanomaterials in tumor treatment, dissecting their working mechanisms, and integrating the latest scientific advancements to predict future development trends. This approach, which combines viral therapy with the application of nanomaterials, represents an innovative and more effective treatment strategy, offering new perspectives in the field of tumor therapy.

Keywords: combined application; drug carriers; nanomaterials; therapeutic viruses; tumor treatment.

Figure 1

Schematic Diagram of CAR-T Structure. CAR typically consists of the following key components. ➀ Antigen Recognition Structure: this part is located outside the cell and is capable of recognizing and binding to specific antigens on tumor cells. It usually originates from the variable region of antibodies and has high antigen specificity. ➁ Transmembrane Segment: this part is a protein fragment that is responsible for anchoring the CAR to the T-cell membrane. ➂ Signal Transmission Segment: this part is located inside the cell and can trigger activation signals in T-cells. The original CAR had only one signal transmission domain, known as the CD3ζ chain, which came from the T-cell receptor complex. In the subsequently developed second and third-generation CARs, one or more co-stimulatory domains, such as CD28 or 4-1BB, were added. These co-stimulatory domains can enhance T-cell activity and longevity.

Figure 2

Tumors are capable of creating an immunosuppressive environment, effectively evading the surveillance of the immune system, and thereby facilitating growth, dissemination, and metastasis. For instance, they could alter their surface proteins to evade recognition by the immune system or secrete immunosuppressive molecules such as cytokines (like TGF-β and IL-10) to directly inhibit the activity of immune cells. Tumor cells can even recruit and activate certain immunosuppressive cells, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs). These cells can suppress immune cells, preventing them from attacking the tumor. Presently, OVs primarily employ two strategies to break through this immunosuppressive environment. (A), Direct cell lysis. OVs selectively infect tumor cells, leading to their lysis and the release of more antigens, which further intensifies the immune response and specifically induces tumor cell apoptosis. (B), Gene therapy. For example, OVs carrying the GM-CSF gene infect tumor cells in large numbers, causing the tumor cells to express GM-CSF. This recruits immune cells such as dendritic cells and macrophages, induces immune infiltration, and destroys pathogens or tumor cells that have been marked by antibodies.

Figure 3

The microenvironments of ‘cold’ and ‘hot’ tumors greatly differ. Cold tumors usually lack effective T-cell infiltration and might lack tumor-specific antigens, making it challenging for the immune system to recognize and attack these tumors. Moreover, the microenvironment of cold tumors may be rich in immunosuppressive cells, such as regulatory T-cells (Tregs), M2 macrophages, and myeloid-derived suppressor cells (MDSCs). These cells further inhibit immune responses, enabling the tumor to more effectively evade the immune system’s attack. Besides, hot tumors typically exhibit substantial immune cell infiltration, particularly tumor-specific T-cells. These tumors usually possess many tumor mutation antigens, making them more easily recognized and attacked by the immune system. Besides T-cells, other immune cell infiltrations, such as B cells, NK cells, dendritic cells, and M1 macrophages, may also be present in hot tumors.

Figure 4

Many studies have employed various novel nanomaterials to ‘precisely guide’ viruses to tumor tissues using elements such as light, heat, magnetism, and pH. It’s akin to equipping the virus with a ‘signal localization’ function that allows it to accurately navigate to the designated location without impacting normal tissues.