Tumor ablation and nanotechnology

Abstract

Next to surgical resection, tumor ablation is a commonly used intervention in the treatment of solid tumors. Tumor ablation methods include thermal therapies, photodynamic therapy, and reactive oxygen species (ROS) producing agents. Thermal therapies induce tumor cell death via thermal energy and include radiofrequency, microwave, high intensity focused ultrasound, and cryoablation. Photodynamic therapy and ROS producing agents cause increased oxidative stress in tumor cells leading to apoptosis. While these therapies are safe and viable alternatives when resection of malignancies is not feasible, they do have associated limitations that prevent their widespread use in clinical applications. To improve the efficacy of these treatments, nanoparticles are being studied in combination with nonsurgical ablation regimens. In addition to better thermal effect on tumor ablation, nanoparticles can deliver anticancer therapeutics that show a synergistic antitumor effect in the presence of heat and can also be imaged to achieve precision in therapy. Understanding the molecular mechanism of nanoparticle-mediated tumor ablation could further help engineer nanoparticles of appropriate composition and properties to synergize the ablation effect. This review aims to explore the various types of nonsurgical tumor ablation methods currently used in cancer treatment and potential improvements by nanotechnology applications.

Figure 1

Comparison of monopolar wet RF (A) with bipolar wet RF (B). The bipolar method does not require a grounding pad and has two saline infusions in the tissue which requires two separate probe insertions. Images courtesy of Dr Afshin Gangi.

Figure 2

A 54-year-old man with colon cancer. A CT scan was obtained 3 months after right hepatectomy (left) shows hepatic 3-cm-diameter metastasis (arrow). A CT scan obtained at the same level 2 months after radiofrequency ablation of tumor (right) shows hypodense “scar.” The scarred area is completely covering the site of the metastasis. Reprinted from de Baere, et al., with permission from the American Roentgen Ray Society.

Figure 3

Heating pattern around a microwave antennae probe where the active heating range extends almost to 2 cm in diameter. A larger active heating range provides a more effective tumor kill, as well as greater efficacy near vasculature. Reprinted from Brace, C.L. with permission from Elsevier.

Figure 4

Illustration of nanoparticle mediated tumor ablation. Nanoparticles containing drug or dye (1) are intravenously injected and extravasate into tumor tissue through the leaky vasculature by the EPR effect (2). Photoirradiation or hyperthermia (3) generate singlet oxygen or facilitates drug release from nanoparticles within the tumor (4) leading to tumor apoptosis and necrosis (5). Radiofrequency (RF), microwave (MW), high intensity focused ultrasound (HIFU), reactive oxygen species (ROS).

Figure 5

Multiple cryoablation probes create a uniform “ice-ball” for full tumor eradication. Illustration courtesy of HealthTronics, Inc, Austin, TX; with permission.

Figure 6

(A) The F-127 magnetic nanoparticle formulation has the ability to be localized using a magnetic field. F-127 Pluronic works to provide a hydrophobic region to carry anti-cancer drugs while still being dispersible in water. (B) The magnetic nanoparticles serve as an effective contrast agent in delineating tumor margins in an MR image. Figure 6B is reprinted from Jain, et al., with permission from Elsevier.