Engineering adipocytes for targeting delivery of triptolide derivative and Ce6 for malignant melanoma cytotoxic-PDT synergistic strategy

Abstract

Malignant melanoma (MM) is an aggressive and easily metastatic cancer that is poorly responsive to current therapy. The crosstalk between melanoma cells and tumor-associated adipocytes (TAA) plays an important role in the progression of MM, which could be leveraged for anticancer treatment. Here, mature adipocytes (Apo) were engineered for encapsulating a palmitic acid-conjugated triptolide derivative (pTP) and photosensitizer Ce6 (named as pTP-Ce6-Apo), to induce a cytotoxic and photodynamic treatment in malignant melanoma. After para-tumor administration, lipolysis releases pTP and Ce6 that is triggered by intracellular glutathione (GSH) and laser irradiation, respectively, subsequently inducing a variety of pathways, inducing the caspase apoptosis program; generation of reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress. Overall, pTP-Ce6-Apo exhibited excellent antitumor performance and high safety, which is desired for MM therapy.

Keywords

• Adipocytes
• Triptolide derivative
• Photodynamic therapy
• Drug delivery
• Malignant melanoma