Combined Photothermal and Ionizing Radiation Sensitization of Triple-Negative Breast Cancer Using Triangular Silver Nanoparticles

Abstract

Background Ionizing radiation (IR) is commonly used in triple-negative breast cancer (TNBC) treatment regimens. However, off-target toxicity affecting normal tissue and grueling treatment regimens remain major limitations. Hyperthermia is one of the greatest IR sensitizers, but only if heat is administered simultaneously or immediately prior to ionizing radiation. Difficulty in co-localizing ionizing radiation (IR) in rapid succession with hyperthermia, and confining treatment to the tumor have hindered widespread clinical adoption of combined thermoradiation treatment. Metal nanoparticle-based approaches to IR sensitization and photothermal heat generation may aid in overcoming these issues and improve treatment specificity. Methods We assessed the potential to selectively treat MDA-MB-231 TNBC cells without affecting non-malignant MCF-10A breast cells using a multimodal approach based upon combined photothermal therapy, IR sensitization, and specific cytotoxicity using triangular silver nanoparticles (TAgNPs) with peak absorbance in the near-infrared light (NIR) spectrum. Results We found that TAgNP-mediated photothermal therapy and radiosensitization offer a high degree of specificity for treatment of TNBC without affecting non-malignant mammary epithelial cells. Discussion If given at a high enough dose, IR, heat, or TAgNPs alone could be sufficient for tumor treatment. However, when the dose of one or all of these modalities increases, off-target effects also increase. The challenge lies in identifying the minimal doses of each individual treatment such that when combined they provide maximum selectivity for treatment of TNBC cells with minimum off-target effects on non-malignant breast cells. Our results provide proof of concept that this combination is highly selective for TNBC cells while sparing non-malignant mammary epithelial cells. This treatment would be particularly important for patients undergoing breast conservation therapy and for treatment of invasive tumor margins near the periphery where each individual treatment might be at a sub-therapeutic level.

Metal nanoparticles as a promising technology in targeted cancer treatment

“…There were no nonmalignant mammary epithelial cells saved as a result of this combination. It was shown that thermal radiation sensitization using triangular silver NPs resulted in excellent results despite the lower treatment dose and frequency (Sears et al., 2021 ), excellent results despite the lower treatment dose and frequency (Sears et al., 2021 ). When combined with the histone deacetylase inhibitor SAHA, gold NPs and radio sensitization were tested in 2D and 3D cancer cell cultures.…”

Metal-Based Nanostructured Therapeutic Strategies for Glioblastoma Treatment—An Update

“…Although effective for shrinking tumors, LITT is non-curative due to difficulties in achieving clean margins, treatment of large tumors and minimizing damage to a normal brain while treating invasive GBM cells. Depending upon their size and shape, AgNPs can be designed with plasmon resonance frequencies in the NIR spectrum, enabling them to generate heat when excited by wavelengths of light emitted by lasers currently used in interstitial thermal therapy of GBM (e.g., 808 nm and 1064 nm) [ 113 , 114 , 115 ]. One challenge to using AgNPs for photothermal therapy is that they are rapidly etched in biological environments, altering their shape and decreasing their efficiency at converting light to heat.…”

“…Furthermore, heat itself is a radiosensitizer when given concurrently or immediately prior to ionizing radiation exposure [ 118 ]. Although not yet tested for use in GBM, preclinical studies using AgNPs for combined photothermal treatment and radiation sensitization of breast cancer indicate that the combined sensitizing effects of AgNPs, heat and radiation can selectively kill cancer cells without killing normal cells [ 115 ]. Furthermore, intratumoral injection of AgNPs (10 ug/cm 3 based upon tumor volume) significantly sensitized intracranial C6 glioma tumors in rats to hyperthermia generated by the excitation of superparamagnetic iron oxide nanoparticles (3 mg/cm 3 ) (see Section 2.3 below), indicating that AgNPs may also sensitize GBM to heat-based treatments [ 119 ].…”

Advances of Nanomedicine in Radiotherapy

“…Recently, noble metal nanoparticles, such as Au-based nanocomposites, have been extensively explored for the synergistic therapeutics of PTT and RT due to their strong NIR optical absorption [96][97][98][99][100][101][102]. For instance, Sun et al wrapped gold nanorods with tumor cell membranes to form novel nanocomposites (GNR@Mem).…”