Nanoparticle-mediated hyperthermia in cancer therapy

Abstract

A small rise in tumor temperature (hyperthermia) makes cancer cells more susceptible to radiation and chemotherapy. The means of achieving this is not trivial, and traditional methods have certain drawbacks. Loading tumors with systematically asministered energy-transducing nanoparticles can circumvent several of the obstacles to achieve tumor hyperthermia. However, nanoparticles also face unique challenges prior to clinical implementation. This article summarizes the state-of-the-art current technology and discusses the advantages and challenges of the three major nanoparticle formulations in focus: gold nanoshells and nanorods, superparamagnetic iron oxide particles and carbon nanotubes.

Figure 1. Methods of achieving tumor hyperthermia

AMF: Alternating magnetic field

Figure 2. Relative scale of synthetic nanomaterials as compared with naturally occurring biomacromolecules and cells

MWNT: Multiwalled carbon nanotubes; RBC: Red blood cell; SPION: Superparamagnetic iron oxide nanoparticle; SWNT: Single-walled carbon nanotubes.

Figure 3. Effects of nanoparticle-mediated hyperthermia on tumors in vivo.

(A) In mice with subcutaneously inoculated human colorectal cancer cells, 90 min following a single 10 Gy dose of radiation therapy using 125 kV x-rays, hematoxylin and eosin-stained slides of the tumor core show minimal necrosis (left), but addition of gold nanoshell-mediated hyperthermia (41°C for 20 min immediately prior to radiation) results in significantly more necrosis (right). Arrows denote size of areas of necrosis within tumors [35]. (B) On further investigation, the tumor core of mice treated with radiation alone (left) has classical tissue architecture with central vascular channels surrounded by orderly layers of cells with decreasing levels of oxygenation with increasing distance – hypoxic areas (further from vasculature) are stained green and perfused areas are stained blue in this immunofluorescence image. However, the mice treated with combined hyperthermia and radiation (right) have tumor cores with complete disruption of normal stromal structure, suggestive of vascular collapse [35]. (C) In a mouse model of breast cancer, treatment with a single dose of 6 Gy with or without post-treatment hyperthermia (42°C for 20 min) was followed by tumor digestion 48 h later and re-implantation in syngeneic mice in limiting dilutions. For reappearance of tumors, the combined treatment group required more cells re-implanted in mice than the radiation alone group, suggestive of a greater effect of combined treatment on putative cancer stem cells. Furthermore, the tumors reappeared as a more aggressive phenotype in the radiation alone group (left) than the combined treatment group (right). These results suggest that more efficient elimination of cancer stem cells by nanoshell-mediated hyperthermia and radiation compared with radiation alone results in lesser ability to recreate tumors as well as appearance of more differentiated, less aggressive and more treatable tumors [46]. Figures reproduced with permission from the referenced sources.