Thermosensitive Nanosystems Associated with Hyperthermia for Cancer Treatment

Abstract

Conventional chemotherapy regimens have limitations due to serious adverse effects. Targeted drug delivery systems to reduce systemic toxicity are a powerful drug development platform. Encapsulation of antitumor drug(s) in thermosensitive nanocarriers is an emerging approach with a promise to improve uptake and increase therapeutic efficacy, as they can be activated by hyperthermia selectively at the tumor site. In this review, we focus on thermosensitive nanosystems associated with hyperthermia for the treatment of cancer, in preclinical and clinical use.

Keywords: cancer treatment; hyperthermia; thermosensitive systems.

Figure 1

Ablation and mild hyperthermia induce distinct cell injury based on the intensity and duration.

Figure 2

Mechanism of drug release from thermosensitive liposomes. (A) Schematic illustration of the mechanism of phase transition of the lipids that form the liposome bilayer. The increase of the temperature above the transition phase temperature (47 °C) leads to higher bilayer permeability, and consequently, the drug release is favored. (B) Amphiphilic molecules forming lamellar structures and their transition phase temperatures. Tc: Phase transition temperature.

Figure 3

Anatomical MRI of tumor-bearing rats in the small animal HIFU setup (upper row) and T1 maps of the tumor and leg overlaid on the anatomical images at different time points: Before the TSL injection, after the first hyperthermia period (t = 20 min), after the second hyperthermia period (t = 40 min), and 70 min after TSL injection. Left: HIFU-treated tumor showing a large T1 response (rat 1); middle: HIFU-treated tumor showing a less sensitive response (rat 2); right: Untreated tumor (no HIFU, rat 4). Reproduced with permission from [107].

Figure 4

Experimental set-up for mild hyperthermia in rabbit V × 2 tumors using a clinical MRI–HIFU system. Axial survey image of a rabbit on top of a water-filled animal adaptor. A waterproofed receive-only imaging coil is fitted around the lower leg. The bottom film of the animal adaptor is coupled to the window of the clinical HIFU system by a gel pad; the HIFU transducer is in the oil bath below. Overlays indicate the relative size of the ultrasound beam path (dashed) and treatment cell (shaded). Right: Rendering of the animal adaptor designed for the clinical HIFU system. The detachable lid (A) is a polyimide film glued to an acrylic ring. The cylindrical water bath (B) is a 3D-printed shell that holds a volume of degassed water, which is heated by water pumped through a coiled channel printed into the walls of the cylinder. Polyimide film (C) forms the base. Reproduced with permission from [108].