The Promise of Nanoparticles-Based Radiotherapy in Cancer Treatment

SIMPLE SUMMARY: Radiotherapy (RT) is used worldwide as a gold standard treatment approach for cancer management. However, the RT treatment modality contains limitations along with numerous side effects. Nanoparticles (NPs) have unique properties that can be utilized in the field of cancer treatment. Therefore, the combination of NPs with RT opens a new arena in cancer treatment. Their synergistic effect strengthens ionizing radiation sensitivity and allows for tumor-selective treatment while reducing side effects. More importantly, NP-based RT offers greater control over RT alone and has shown higher selectivity. In addition, the combined treatment also helps to overcome radioresistance and drug-resistance phenomena. The main mechanism through which NP-based RT destroys cancer cells includes production of ROS, which damage DNA, inhibiting the DNA-repair system, perturbing the cell cycle, and controlling the tumor microenvironment. NP-based RT has been reported to destroy cancer stem cells and has shown good results in clinical trials. Moreover, the addition of phototherapy to NP-based RT reduces the limitations of phototherapy and has shown excellent cancer cell-killing potentiality. ABSTRACT: Radiation has been utilized for a long time for the treatment of cancer patients. However, radiotherapy (RT) has many constraints, among which non-selectivity is the primary one. The implementation of nanoparticles (NPs) with RT not only localizes radiation in targeted tissue but also provides significant tumoricidal effect(s) compared to radiation alone. NPs can be functionalized with both biomolecules and therapeutic agents, and their combination significantly reduces the side effects of RT. NP-based RT destroys cancer cells through multiple mechanisms, including ROS generation, which in turn damages DNA and other cellular organelles, inhibiting of the DNA double-strand damage-repair system, obstructing of the cell cycle, regulating of the tumor microenvironment, and killing of cancer stem cells. Furthermore, such combined treatments overcome radioresistance and drug resistance to chemotherapy. Additionally, NP-based RT in combined treatments have shown synergistic therapeutic benefit(s) and enhanced the therapeutic window. Furthermore, a combination of phototherapy, i.e., photodynamic therapy and photothermal therapy with NP-based RT, not only reduces phototoxicity but also offers excellent therapeutic benefits. Moreover, using NPs with RT has shown promise in cancer treatment and shown excellent therapeutic outcomes in clinical trials. Therefore, extensive research in this field will pave the way toward improved RT in cancer treatment.