Immunogenic Treatment for Metastatic Breast Cancer Using Targeted Carbon Nanotube Mediated Photothermal Therapy in Combination with Anti-PD-1

Abstract

The high prevalence of breast cancer is a global health concern, but there are no safe or effective treatments for it at its advanced stages. These facts urge the development of novel treatment strategies. Annexin A5 (ANXA5) is a natural human protein that binds with high specificity to phosphatidylserine, a phospholipid tightly maintained in the inner leaflet of the cell membrane on most healthy cells but externalized in tumor cells and the tumor vasculature. Here, we have developed a targeted photosensitizer for photothermal therapy (PTT) of solid tumors through the functionalization of single walled carbon nanotubes (SWCNTs) to ANXA5—the SWCNT-ANXA5 conjugate. The ablation of tumors through the SWCNT-ANXA5-mediated PTT synergizes with checkpoint inhibition, creating a systemic anti-cancer immune response. In vitro ablation of cells incubated with the conjugate promoted cell death in a dose-dependent and targeted manner. This treatment strategy was tested in vivo with the orthotopic EMT6 breast tumor model in female balb/cJ mice. Enhanced therapeutic effects were achieved by using intratumoral injection of the conjugate and treating tumors at a lower PTT temperature (45oC). When combined with checkpoint inhibition of anti-PD-1, SWCNT-ANXA5-mediated PTT increased survival and 80% of the mice survived for 100 days. Evidence of immune system activation by flow cytometry of splenic cells strengthens the hypothesis of an abscopal effect as a mechanism of prolonged survival.

Special Section on Nanotherapeutics in Cancer Research—Editorial

“…A following review by Towner, Dissanayake, and Ahmed outlines clinical advances of lead compound PLGAbased NPs for metastatic triple-negative breast cancer (TNBC) as well as current clinical therapies that may be beneficial when combined with NP composites (Towner et al, 2024). In keeping with the breast cancer theme, an in vitro and preclinical in vivo research study in mice by Harrison and his group presents a photothermal therapy using anti-PD-1-targeted carbon nanotubes as a potential treatment strategy for metastatic breast cancer (Faria et al, 2024); which is followed by an in vitro research investigation by Ahmed and her group that focuses on the use of biocompatible polydopamine core-shell NPs as a potential therapy for breast cancer (Steeves et al, 2024).…”