Radiosensitizers, Nanotherapeutics, Nanoparticle Albumin-Bound Paclitaxel

Nanotechnology -based diagnostic tools have already entered our clinical practice. Certain molecules circulating in the blood, which we call tumor markers, can now be detected much more sensitively and earlier using nanoparticles (NTs). For example, a new biological barcode assay using gold NTs has been developed to detect prostate-specific antigen (commonly known as PSA). This assay detected PSA increases more sensitively, enabling better identification of patients requiring salvage radiotherapy after prostate surgery.

• What are nanoparticles, and what are their examples? Nanotechnology in cancer diagnosis

Microvesicles released into the bloodstream by gblioblastomas, a type of brain tumor cell, have been detected using NT-based methods, providing insight into the disease's recurrence potential and treatment response.

Nanotechnology has also been incorporated into devices developed to capture "circulating tumor cells." These are cells shed from the primary tumor into blood vessels that enter the bloodstream. By seeding additional tumors (metastases) in vital distant organs, they trigger a mechanism responsible for many cancer-related deaths. Tools that detect circulating tumor cells allow real-time disease monitoring and early diagnosis. Another important aspect of these cells is their potential to enable real-time treatment response assessment in radiation oncology.

Inorganic Nanoparticles and Radiosensitizers

There has long been interest in radiosensitizers. Radiosensitizers are drugs that make tumor cells sensitive to radiotherapy to increase its effectiveness. Chemotherapy and targeted drugs can be used for this purpose. One particular strategy is to increase the radiation dose within tumor tissue using high-atomic-number materials. The radiation dose absorbed by any tissue is related to the material's high atomic number. The aim is to provide a higher radiation dose to tumor tissue while delivering a lower dose to adjacent normal tissue. Many studies have used gold NTs as radiosensitizers for this purpose. Gold has a high atomic number and an inert (inactive), safe profile, having previously been used safely in medical treatments. However, direct injection into the tumor currently appears to be the safest route for these agents.

Nanotherapeutics to Increase the Effectiveness of Chemoradiotherapy

Chemoradiotherapy, the combined administration of chemotherapy and radiotherapy, has long been an important treatment option in oncology. It has prolonged survival and improved disease control, but causes more side effects than other treatment options. Ideally, treatment aims to increase chemoradiotherapy effectiveness while reducing side effects. As previously discussed, NTs have many important characteristics for carrying chemotherapy drugs, such as preferential accumulation in tumors and inability to penetrate (adhere to) normal vessels. These properties allow lower drug doses to reach normal tissue, reduce side effects, and provide slow, controlled drug delivery.

Liposomal formulations of the chemotherapy drug doxorubicin were the first NT therapeutic developed for cancer treatment. This is a form of doxorubicin encapsulated in a pegylated (polyethylene glycol-coated) liposome. The drug was developed to treat Kaposi sarcoma (in this AIDS-associated disease, lesions grow on the skin, inside the mouth, nose, throat, and other organs). Liposome-coated doxorubicin is less cardiotoxic than conventional doxorubicin. Liposomal doxorubicin is also used to treat ovarian cancer and multiple myeloma.

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), is a recently approved nanoparticle chemotherapeutic. It has contributed positively to the treatment of pancreatic, breast, and ovarian cancers. It also has radiosensitizing properties, allowing the administered radiation dose to be reduced by up to %50.

Polymeric NT formulations of the chemotherapy drugs paclitaxel and docetaxel have begun to be tested with radiotherapy in non-small cell lung cancer.

In addition, NT formulations of certain drugs that could not be used as small molecules because of severe toxicity have begun to be used with far fewer side effects and high effectiveness. For example, wortmannin is a radiosensitizer that suppresses DNA repair. Its NT formulation is tolerated 3-5 times better than its small-molecule form.

Radiation-Mediated Drug Delivery Systems Using NTs

Radiotherapy can be used to facilitate NT therapeutics reaching the tumor. Ionizing radiation can increase the permeability of tumor-feeding vessels and produce the previously discussed EPR effect (enhanced permeability and retention (EPR) effect). When exposed to sufficiently high-energy radiation, atoms become ionized; this is called ionizing radiation. Electrons can thereby be stripped from atoms, forming ions. Living cells, and more importantly their DNA, are damaged by this ionization. Radiotherapy works on this principle: damaging tumor cell DNA triggers tumor cell death.

Studies have indeed shown that radiotherapy increases NT therapeutic accumulation in tumors. This preferential accumulation effect may subsequently be transformed into an effective treatment through hyperthermia-triggered drug release .

Available data and studies suggest that radiation-mediated drug delivery may be a new strategy in cancer treatment .

The Future

Advances in cancer treatment have paralleled technological developments. For example, a major development in radiation oncology, intensity-modulated radiation therapy (intensity-modulated radiation therapy), became possible through advances in physics and computer science. It is almost certain that nanotechnology will be a major driving force in future oncology advances.

In summary, NT-based drugs may increase radiotherapy effectiveness, improve recognition of metastatic lymph nodes, enable personalized treatment, and promise fewer side effects while increasing the effectiveness of chemotherapy drugs.