Enhanced anti-tumor efficacy of temozolomide-loaded carboxylated poly(amido-amine) combined with photothermal/photodynamic therapy for melanoma treatment

Abstract

Chemotherapy is an important treatment for malignant tumors; however, its efficacy and clinical application are limited by its side effects and drug resistance properties. Chemotherapy and phototherapy exhibit synergistic anti-tumor effects. In the present study, a carboxylated poly(amido-amine) (PAMAM) with low cytotoxicity was synthesized as a delivery nanocarrier for loading chemotherapeutic drugs, temozolomide (TMZ), and fluorescent dye indocyanine green (ICG). Hyaluronic acid (HA), which targets the CD44-overexpressing cancer cells, was modified on the nanocarrier surface to enhance the selective killing of melanoma cells. Temperature effect and singlet oxygen production experiments showed that the ICG-loaded nanoparticles exhibited good capability to generate heat and singlet oxygen under near-infrared (NIR) light (808 nm) irradiation. In vivo imaging measurement confirmed that the ICG-encapsulated nanoparticle was delivered successfully and effectively accumulated in the tumor site. In vitro and in vivo experiments revealed that the joint application of TMZ- and ICG-loaded nanoparticle can kill melanoma cells and suppress growth after NIR light irradiation. Thus, HA-modified carboxylated PAMAM loaded with TMZ and ICG serves as a promising nanoplatform for melanoma treatment.

Keywords: Indocyanine green; Melanoma; Photodynamic therapy; Photothermal therapy; Temozolomide.