Serena Duchi
ISOF-CNR,Italy
Title: Mesenchymal Stromal Cells and therapeutic nanoparticles as multimodal treatment of osteosarcoma
Biography
Biography: Serena Duchi
Abstract
Clinical problem: Osteosarcoma (OS) is a highly malignant primary bone tumor and the most frequent bone sarcoma in children and adolescents [1]. Standard treatments include surgery and chemotherapy. The current survival rate is 65%. The poor outcome is mostly due to an inability to deliver drugs to the infiltrative tumor cells. Therefore, significant efforts need to be undertaken to develop new delivering strategies. One approach is to dispense therapeutic agents using Mesenchymal Stromal/Stem Cells (MSC) which have the unique ability to home and engraft in the tumor stroma. They therefore represent an ideal vehicle for targeted drug delivery [2].
Our aim is to evaluate the efficacy of MSC as delivery vehicle for a bimodal treatment consisting of photodynamic therapy (PDT) [3], and of the cytostatic drug Paclitaxel (PTX) [4].
Methodology: We engineered biodegradable nanoparticles (NPs) able to induce cell death through a dual synergic action (PTX and PDT). Then we loaded these NPs into MSC and we used these cells as a Trojan horse vehicles. Albumin (HSA) and Keratin (Ker) based NPs were conjugated with the photosensitizer chlorin e6 (Ce6), and the PTX was introduced through desolvation or drug-induced protein self-assembly techniques. Human MSC were loaded with different dosages of NPs, co-cultured with different OS tumor cell lines and irradiated with infrared light. Results show that MSC efficiently internalize NPs, release PTX by exocytosis and after irradiation generate ROS, inducing an overall 90% mortality of tumor cells.